MEDICAMENT FOR LIVER REGENERATION AND FOR TREATMENT OF LIVER FAILURE

Abstract

The present invention relates to the use of a compound which inhibits the activity of MKK4 as a medicament for the treatment of a patient suffering from an impaired liver function, to the use of a compound as a medicament for the treatment of liver failure, including acute/fulminant or chronic liver failure and/or for increasing the regeneration of liver tissue in a patient.

Description

PRIORITY CLAIM

[0001] This application is a continuation of U.S. patent application Ser. No. 14/875,879 filed Oct. 6, 2015, pending, which is a continuation of U.S. patent application Ser. No. 14/009,738 filed Dec. 23, 2013, now U.S. Pat. No. 9,186,381 issued Nov. 17, 2015, which is the national stage under 35 USC .sctn. 371 of Patent Cooperation Treaty Application Number PCT/EP2012/056481 filed on Apr. 10, 2012, which claims priority under 35 U.S.C .sctn. 365 and applicable treaties from U.S. provisional application Ser. No. 61/473,015 filed Apr. 7, 2011, from EP application no 11161588.6 filed Apr. 7, 2011, and from EP application no. 11167373.7 filed May 24, 2011, the entire disclosures of these applications are incorporated herein by reference.

BACKGROUND ART

[0002] The present invention relates to the use of a compound as a medicament for the treatment of a patient suffering from an impaired liver function, to the use of a compound as a medicament for the treatment of liver failure, including acute/fulminant or chronic liver failure and/or for increasing the regeneration of liver tissue in a patient. Also, the invention relates to the use of the compound to increase the robustness and regeneration of cultured hepatocytes in vitro to improve cell based therapies, e.g. to a process for cultivating hepatocytes in the presence of the compound, including the use of the cultivating hepatocytes as a transplant, and for hepatocyte transplantation, respectively, into a patient suffering from liver failure. Further, the invention relates to the use of the compound for the production of the medicament, and to the use of hepatocytes cultured in vitro in the presence of the compound for the production of a hepatocyte transplant.

[0003] Further, the invention relates to a bio-artificial liver comprising cutlivated hepatocytes which contain or are contacted by the compound which can be used as a medicament. Further, the invention relates to a process for producing hepatocytes which comprise the compound used as a medicament, and to the use of cultivated hepatocytes being contacted by the medicament for use as a medicament in the treatment of a functionally impaired liver, for the treatment of liver failure, and/or for supporting liver regeneration. Liver failure which can be treated according to the invention includes acute and/or fulminant hepatitis due to infection with hepatotropic viruses, alcohol abuse, obesity, genetic diseases like Wilson's disease, hemochromatosis, alpha1-antitrypsin deficiency and related conditions. Liver failure which can be treated according to invention also includes all forms of chronic liver failure with liver cirrhosis induced by e.g. the causes as indicated above.

STATE OF THE ART

[0004] To-date, liver failure is treated by transplantation of a donor liver, however there is a severe shortage of donor organs.

[0005] WO98/39352, WO99/14226, and U.S. Pat. No. 7,569,575 B2 describe use and synthesis of locked nucleic acids (LNA).

OBJECTS OF THE INVENTION

[0006] It is an object of the invention to provide a medicament suitable for the treatment of insufficient liver function, e.g. liver failure, and to provide cultivated hepatocytes, which can be kept in culture for use in a bio-artificial liver, e.g. for use in the purification of blood or for transplantation into patients with impaired liver function.

GENERAL DESCRIPTION OF THE INVENTION

[0007] The invention achieves the objects by the features of the claims, and especially by providing a compound inhibiting or inactivating the mitogen-activated protein kinase kinase 4 (MAP2K4, also termed MKK4). The nucleotide sequence of the mRNA encoding human MKK4 according to accession No. NM_003010 is given as SEQ ID NO: 1204. Inhibition or inactivation of the activity of MKK4 can be by reduction of the expression of MKK4, e.g. by RNA interference induced by siRNA, especially shRNA or microRNA hybridizing to the mRNA encoding MKK4, or by inhibition of MKK4 present in a hepatocyte, e.g. by a kinase-specific inhibitor compound like SP600125, myricitine, Genistein, and PD98059.

[0008] The invention is based on the finding that the reduction or deletion of active MKK4 in hepatocytes, which can be both cultivated hepatocytes in vitro and hepatocytes of a liver of an animal or human patient, results in increased regeneration of hepatocytes, e.g. in extended cultivation periods and in an increase of regeneration of a damaged or impaired liver in vivo, e.g. in experimental animals after induction of an experimental liver failure representing liver failure in a human patient. It has been found that the reduction or deletion of active MKK4 in hepatocytes can result in an increased proliferative capacity due to an earlier cell cycle entry and in an increased resistance against apoptosis. In summary, contacting hepatocytes in vivo by the compound inhibiting or inactivating MKK4 results in an increased survival of mice in experimental models of liver failure. Further, contacting cultured hepatocytes in vitro by the compound inhibiting or inactivating MKK4 results in extended cultivation periods and in production of cultivated hepatocytes, which can be used as a medicament, e.g. as a transplant, or which can be used as part of a device for the continuous purification of blood withdrawn from and returned to a patient.

[0009] Inactivation or deletion of MKK4 can be obtained by preventing the expression of functional MKK4 in liver cells, e.g. by inactivating the endogenous gene encoding MKK4, e.g. by insertional mutagenesis of the endogenous gene encoding MKK4, e.g. by inserting a nucleotide sequence comprising at least one nucleotide, for disruption of the endogenous gene encoding MKK4, by preventing translation of the mRNA encoding MKK4, or by pharmacological means, e.g. by contacting hepatocytes in vivo or in vitro by a compound which inhibits the kinase function MKK4.

[0010] Preferably, inactivation of MKK4 is obtained by reduction or prevention of expression of MKK4 by administration of an inhibitory RNA through RNA interference (RNAi), which is e.g. an oligonucleotide hybridizing to the mRNA encoding MKK4, which inhibitory RNA can e.g. be an siRNA, an siRNA or any form of shRNA contained in a microRNA, e.g. a microRNA based shRNA, an antisense oligonucleotide, or a mixture of these. Preferably, the oligonucleotide hybridizing to the mRNA encoding MKK4 comprises or consists 19, 21 or 22 nucleotides which are complementary, especially under physiological and cellular conditions, to the mRNA sequence encoding MKK4, and a second section, e.g. an antisense strand, which is complementary in sequence to the first section. From such a double-stranded siRNA molecule, in a cellular environment, the first section is released from the second section and binds to the mRNA encoding MKK4 to induce the degradation of this mRNA or to induce inhibition of translation. Double stranded RNA molecules (siRNAs) which later release one section for mRNA targeting can be directly delivered into livers or liver cells but can also be contained in shRNAs or miRNAs from which the double stranded RNA is later released by enzymatic processing though the cellular RNAi machinery. The sequence of the oligonucleotide hybridizing to the mRNA encoding MKK4 to induce its degradation or to prevent its translation can be 100% complementary in sequence as usually is the case with siRNAs or shRNAs, but also can contain mismatches as is often the case with endogenous miRNA, e.g. endogenous miR-15b, miR-24, miR-25, and miR-141, which are also included as compounds for use in the invention, can target MKK4 mRNA with being only partially complementary in sequence. In the description, exemplary oligonucleotide sequences which are hybridizing to the mRNA encoding MKK4 are give, which oligonucleotides can be contained in an siRNA, e.g. as a first section, preferably forming a double-strand with a reverse complementary second section contained in the siRNA.

[0011] It has been found that inactivation of MKK4 activity, preferably by reduction or inhibition of the expression of MKK4 by presence of an oligonucleotide hybridizing to the mRNA encoding MKK4, can be obtained by contacting hepatocytes in vivo or in vitro with at least one oligonucleotide specifically hybridizing to the mRNA encoding MKK4. Contacting in hepatocytes the mRNA which encoded MKK4 can be obtained by administrating to a human or animal patient the RNA hybridizing to the mRNA encoding MKK4 using RNAi through siRNAs by transient in vivo transfection of the siRNA, or alternatively by using, e.g. as a medicament, any means of stable delivery of siRNA, e.g. shRNA, especially microRNA based shRNA or antisense oligonucleotides which are hybridizing to the mRNA encoding MKK4, e.g. use of a viral or transposon-based nucleic acid construct which contains an expression cassette encoding the shRNA, for transcription of the shRNA from the expression cassette. The siRNA, or the nucleic acid construct containing an expression cassette encoding the siRNA, is used as a medicament. The nucleic acid construct can e.g. be a viral vector or a transposon-containing nucleic acid construct additionally encoding transposase for integrative stable transduction.

[0012] Generally, an oligonucleotide hybridizing to the mRNA encoding MKK4 for reducing or preventing the expression of MKK4 in a liver cell is an oligonucleotide having a sequence hybridizing to the mRNA encoding MKK4, especially hybridizing to SEQ ID NO: 1204, under physiological conditions, e.g. in the cellular environment of a liver cell. The sequence can be fully complementary, i.e. be reverse complementary to a section of the mRNA of SEQ ID NO: 1204, or the sequence can have mismatches as it often occurs in microRNA mediated inhibition of translation, e.g. the oligonucleotide sequence has a nucleotide sequence of at least 80%, preferably of at least 85%, more preferably of at least 90% or of 95% identity to a reverse complementary section SEQ ID NO: 1204, including as examples the endogenous miRNAs miR-15b, miR-24, miR-25, and miR-141.

[0013] Preferred inhibitory oligonucleotides, e.g. shRNA, comprise or consist of one or more of the following oligonucleotides: SEQ ID NO: 1 to SEQ ID NO: 1203. For the design of these sequences the DSIR tool for siRNA and shRNA target design (BMC Bioinformatics, 2006 Nov 30; 7(1):520.) with a score threshold of 70 was used, and therefore all SEQ ID NO: 1 to 1203 have score of at least 70. Inhibitory oligonucleotide sequences, and groups of inhibitory oligonucleotide sequences having higher scores are preferred. The sequences are given in an order of descending score value, e.g. SEQ ID NO: 1 has the highest score (107.1), and SEQ ID NO: 1200, SEQ ID NO: 1201, SEQ ID NO: 1202, and SEQ ID NO: 1203 have the lowest score (70.0 each). SEQ ID NO: 1 to SEQ ID NO: 11 have a score of at least 100, SEQ ID NO: 12 to SEQ ID NO: 55 have a score of at least 95.1, e.g. of 99.8 to 95.1, SEQ ID NO: 56 to SEQ ID NO: 136 have a score of at least 90.0, e.g. of 94.8 to 90.0, SEQ ID NO: 137 to SEQ ID NO: 317 have a score of at least 85, e.g. of 89.9 to 85.0, SEQ ID NO: 318 to SEQ ID NO: 593 have a score of at least 80, e.g. of 84.9 to 80.0, SEQ ID NO: 594 to SEQ ID NO: 915 have a score of at least 75.0, e.g. of 79.9 to 75.0, and SEQ ID NO: 916 to SEQ ID NO: 1203 have a score between 74.9 and 70.0. Further, shRNA or microRNA molecules can comprise one of these oligonucleotides which are complementary to the mRNA encoding MKK4, e.g. comprising one of these oligonucleotides as a first section and a complementary second section in the siRNA as hybridizing sections in a microRNA.

[0014] The oligonucleotides hybridizing to the mRNA encoding MKK4 for use as a medicament for the regeneration of liver tissue, or for the treatment of liver failure, liver insufficiency and/or liver cirrhosis, can preferably be in the form of RNA, DNA, or hybrids of DNA and RNA, peptide-linkage nucleic acids (PNA), and nucleic acid derivatives containing a ribose moiety with substituents bridging the 2'-carbon atom and the 4'-carbon atom, e.g. by an oxymethylene group or an aminomethylene group, which derivatives are termed locked nucleic acids (LNA), including further derivatives of the phosphate-sugar backbone, single-stranded, preferably double-stranded, which by intracellular processing by the RNAi enzymatic machinery release a single stranded oligonucleotide for hybridization to the mRNA encoding MKK4.

[0015] In the alternative to consisting of the use of a nucleic acid sequence hybridizing to the mRNA encoding MKK4, e.g. for direct use as a medicament, the inhibitory RNA can be contained as a coding sequence under the control of a promoter in an expression cassette. Depending on the promoter, which can be a constitutive or an inducible promoter, upon introduction into the hepatocyte the inhibitory RNA is produced by transcription.

[0016] For introduction of nucleic acid constructs reducing or deleting the expression of active MKK4, e.g. nucleic acid constructs which interrupt the endogenous gene encoding MKK4 of a hepatocyte or inhibitory RNA hybridizing to the mRNA encoding MKK4, the nucleic acid constructs are preferably provided in the form of one or more oligonucleotides in a pharmaceutically acceptable carrier formulation or in the form of a viral vector packaged in a viral particle or in a virus-like particle. A viral vector can be a retroviral, a lentiviral vector, an adeno-associated viral vector, or adenoviral vector.

[0017] A formulation of the compounds or compositions of the invention for inhibiting or inactivating MKK4 in a pharmaceutically acceptable carrier can e.g. be in a formulation of lipid nanoparticles (LNP) (as e.g. available from Alnylam Pharmaceuticals, USA), a liposome formulation, and/or in a formulation containing a combination with at least one transfection enhancing agent, e.g. lipofectamine and/or as a Calcium complex.

[0018] In the alternative or in addition to an oligonucleotide having a sequence hybridizing to the mRNA encoding MKK4, e.g. an RNAi hybridizing to the mRNA encoding MKK4, agents inactivating the activity of MKK4, e.g. agents blocking the formation of MKK4 protein, can be used as compounds for use as a medicament according to the invention. Exemplary compounds suitable for inactivating MKK4 are e.g. SP600125, myricitine, Genistein, and PD98059, especially for use as medicaments for the treatment of liver failure, and for the regeneration of liver tissue, respectively.

[0019] Histologic analysis of mouse livers with stable knock down of MKK4, experimentally generated by transfection with a nucleic acid construct containing an expression cassette for shRNA hybridizing to the mRNA encoding MKK4 showed normal histology. Further, no increase in neoplasms was detected in the experimental animals, indicating that deletion of MKK4 does not augment the risk of cancer development.

DETAILED DESCRIPTION OF THE INVENTION

[0020] The invention is now described in greater detail by way of examples with reference to the figure, which show in

[0021] FIG. 1 schematic representations of nucleic acid constructs for producing inhibitory RNA,

[0022] FIG. 2 a schematic representation of a transposase mediated intrahepatic transfer of an expression cassette encoding an inhibitory RNA (micro RNA based shRNA) of the invention,

[0023] FIG. 3 the time course of the body weight of mice after stable transposon mediated intrahepatic transfer of an expression cassette for inhibitory RNA and controls, whereas an increase in body weight correlates with an increase in liver repopulation with the construct,

[0024] FIG. 4 GFP-imaging of explanted mouse livers in the process of repopulation by hepatocytes stably expressing shRNA specific for inactivating MKK4,

[0025] FIG. 5 a Western blot specific for MKK4 of liver samples of mice stably transfected with an expression cassette encoding shRNA specific for inactivating MKK4,

[0026] FIG. 6 immunofluorescence analysis of the livers of mice stably transfected with expression cassette encoding shRNA specific for inactivating MKK4,

[0027] FIG. 7 a Western blot for cyclin A and E of nuclear liver extracts of transfected mouse livers in the indicated time course after partial hepatectomy indicating earlier cell cycle entry of hepatocytes stably expressing shRNA specific for MKK4,

[0028] FIG. 8 a Ki67 staining of mouse livers expressing shRNA specific for MKK4 or control shRNA at the indicated time points after partial hepatectomy,

[0029] FIG. 9 a quantifying graph of Ki67 positive hepatocytes depicted in FIG. 8,

[0030] FIG. 10 TUNEL (upper panel) and H&E staining (lower panel) on liver sections after induction of an acute/fulminant liver failure in control shRNA transfected hepatocytes in comparison to hepatocytes expressing an shRNA specific for RNA of MKK4, which are protected,

[0031] FIG. 11 a quantifying graph of apoptotic hepatocytes according to TUNEL staining as depicted in FIG. 10,

[0032] FIG. 12 a survival curve of mice expressing the shRNA inactivating MKK4 (shMKK4) compared to control mice (shCtr.) after induction of liver failure,

[0033] FIG. 13 a quantifying graph of EdU incorporation into cultured murine hepatocytes with inactivated MKK4 activity (FAHIG-shMKK4) and control hepatocytes (FAHIG-shCtr) with an inset showing phase contrast micrographs of these hepatocytes,

[0034] FIG. 14 phase contrast micrographs of cultured hepatocytes with inactivated MKK4 (shMKK4) at day 29 (d29) and of control hepatocytes (shCtr) at day 12 (d12), and at day 3 of hepatocytes replated at day 15 (replating),

[0035] FIG. 15 a survival curve of FAH -/- mice after transplantation of hepatocytes kept one week in culture expressing shRNA specifically inactivating MKK4 or a control shRNA,

[0036] FIG. 16 photographs, GFP-imaging, .alpha.-FAH immunostaining and H&E staining of liver of mice aged for 1 year following transplantation of hepatocytes stably expressing shRNA specifically inactivating MKK4, and in

[0037] FIG. 17 an overview of the inhibitory effect of preferred small inhibitory compounds.

[0038] Using mice and murine liver tissue and hepatocytes as examples, especially representing human patients and human liver tissue and human hepatocytes, respectively, it was found that liver regeneration could be increased by inactivating MKK4 activity both in vivo and in cultured hepatocytes. Mice harbouring livers with reduced MKK4 activity show increased regenerative capacity under conditions of liver failure, which also resulted in an increased survival. Inactivation of MKK4 activity could efficiently be achieved by inhibitory RNA present in hepatocytes, in vivo and in vitro, which inhibitory RNA could be generated by transcription from a stably or transiently transfected nucleic acid construct containing an expression cassette encoding at least one RNA which under physiological conditions hybridizes to the mRNA of MKK4.

[0039] Alternatively, the inhibitory RNA could be introduced, e.g. transfected into hepatocytes in vivo and in culture, e.g. in the form of an siRNA, shRNA or microRNA, preferably in a suitable formulation, e.g. formulated as a liposome preparation or a lipid nanoparticle preparation. In the alternative to the use of inhibitory RNA for use as a medicament for the treatment of liver and hepatocytes, SP600125, myricitine, Genistein, PD98059, 3-(Dimethylamino)-N-[3-[(4-hydroxybenzoyl)-amino]-4-methylphenyl]benzamid- e (ZM 336372), 2-hydroxy-1-methyl-4-oxo-N-pyridin-4-ylquinoline-3-carboxamide (BAS00525963), 2-(1H-indazol-5-yliminomethyl)-6-nitrophenolate (BAS00697444), 5-[2-(3,5-dimethyl-1H-pyrazol-4-yl)ethyl]-7-oxo-N-phenyl-1H-pyrazolo[1,5-- a]pyrimidine-3-carboxamide (SYN22174524), 5-[2-(3,5-dimethyl-1H-pyrazol-4-yl)ethyl]-3-(4-fluorophenyl)-1H-pyrazolo[- 1,5-a]pyrimidin-7-one (SYB22174787), 5-[2-(3,5-dimethyl-1H-pyrazol-4-yl)ethyl]-3-(4-methylphenyl)-1H-pyrazolo[- 1,5-a]pyrimidine-7-one (SYN22175977), 3-(4-chlorophenyl)-5-[2-(3,5-dimethyl-1H-pyrazol-4-yl)ethyl]-2-(methoxyme- thyl)-1H-pyrazolo[1,5-a]pyrimidine-7-one (SYN22176267), -[2-(3,5-dimethyl-1H-pyrazol-4-yl)ethyl]-2-(methoxymethyl)-3-(4-methylphe- nyl)-1H-pyrazolo[1,5-a]pyrimidine-7-one (SYN22176367), 5-[2-(3,5-dimethyl-1H-pyrazol-4-yl)ethyl]-2-(3-methoxyphenyl)-3-methyl-py- razolo[5,1-b]pyrimidine-7-ol (SYN22176842), 5-[2-(3,5-dimethyl-1H-pyrazol-4-yl)ethyl]-2-(2-methoxyphenyl)-3-methyl-py- razolo[5,1-b]pyrimidine-7-ol (SYN22176990), 3-(4chlorophenyl)-5-[2-(3,5-dimethyl-1H-pyrazol-4-yl)ethyl]-2-methyl-1H-p- yrazolo[1,5-a]pyrimidine-7-one (SYN22177890), 5-amino-3-[(Z)-1-cyano-2-[3-[(4-methoxy-6-piperidin-1-yl-1,3,5-triazin-2-- yl)oxy]phenyl]ethenyl]-1-(2-hydroxyethyl)pyrazole-4-carbonitrile (BAS00896568), 2-(1H-indazol-5-yliminomethyl)-6-methoxy-4-nitrophenolate (BAS00697462), 7-oxobenzo[e]perimidine-4-carboxylic acid (BAS00368055), the further compounds contained in Table 1 given herein, and combinations thereof could be used as medicaments, the presence of which inactivated MKK4 activity at least partially, also resulting in an increase of hepatocyte proliferation, protection against induced apoptosis, and restoration of liver function. These compounds having specific inhibitory activity against MKK4 are collectively referred to as small inhibitory compounds. Accordingly, both the inhibitory RNA having specificity for the RNA encoding MKK4 and the small inhibitory compounds having specificity for MKK4 protein each inhibit MKK4 and are therefore used as medicaments in the treatment of liver failure and/or for the protection of hepatocytes against apoptosis and/or for the regeneration of hepatocytes. The small inhibitory compounds can be formulated in a pharmaceutically acceptable formulation, comprising e.g. buffer substance and carrier substance as well as formulation additives as known to the pharmacist, e.g. for i.v., i.m., intra-liver administration or oral administration.

[0040] During functional in vitro testing of hepatocytes containing nucleic acid constructs with stable expression of FAH, GFP and shRNA, hepatocytes were isolated from moose livers and cultivated. It was found that only hepatocytes which were transfected with an expression cassette encoding an inhibitory RNA targeting, i.e. specifically hybridizing with, the mRNA encoding MKK4 could be cultivated for extended periods, e.g. for over 30 days. In addition, these hepatocytes could be trypsinized and replated according to standard methods.

[0041] Transplantation of primary hepatocytes expressing the shRNA against MKK4 after 1 week in culture into FAH knock-out mice showed the capacity of the hepatocytes in which MKK4 was inactivated to repopulate the liver of these mice and allow survival. In contrast, this result could not be obtained by primary hepatocytes expressing the shRNA against MKK4 do not undergo major dedifferentiation during the time of culture.

Example 1

Inactivation of MKK4 by Transcription of Inhibitory RNA From an Expression Cassette Integrated Into Liver Tissue

[0042] The introduction of inhibitory RNA into hepatocytes, i.e. into the liver of a patient, for inactivating MKK4 in vivo by expression of the inhibitory RNA from a nucleic acid construct encoding the inhibitory RNA in an expression cassette is shown on the example of mice (C57BL/6) using an expression cassette encoding the inhibitory RNA for production of the shRNA hybridizing in the mRNA encoding MKK4. The promoter controlling transcription of the inhibitory RNA was constitutive.

[0043] in short, homozygous FAH-negative mice (FAH -/-) were kept with constant administration of NTBC in order to block the 4-hydroxyphenylpyruvate dioxygenase which would otherwise lead to the accumulation of toxic metabolites in the liver. As inhibitory RNA, SEQ ID NO: 1 or, alternatively, SEQ ID NO: 2 was used, both of which hybridize with the mRNA encoding MKK4. Each inhibitory RNA was introduced by contacting the liver cells in vivo with nucleic acid constructs with transposase-specific inverted repeat sections (IR) on both termini, containing an expression cassette for FAH for complementation of the FAH -/- genotype upon expression, by hydrodynamic tail vein injection in combination with a second nucleic acid construct encoding transposase sleeping beauty 13 (SB13) under the control of the PGK promoter.

[0044] The nucleic acid constructs are shown in FIG. 1. FIG. 2 schematically shows the steps of the genetic manipulation. A first control construct p/T-FAHIG contains the complementing FAH expression cassette and a green fluorescent protein (GFP) expression cassette comprising the GFP encoding sequence under the control of an IRES element, but encodes no inhibitory RNA. A sequence encoding an inhibitory RNA with no target as a control, which in addition to the GFP expression cassette in 3' to the GFP encoding sequence encodes a microRNA was contained in the construct p/T-FAHIG-shCtr. A sequence encoding an inhibitory RNA according to the invention was contained in construct p/T-FAHIG-shMKK4, which in addition to the GFP expression cassette in 3' to the GFP encoding sequence encodes a microRNA (depicted as a loop) comprising an shRNA as an example for an inhibitory RNA. In the example, SEQ ID NO: 1, alternatively SEQ ID NO: 2 was used as a preferred representative of inhibitory RNA sequences. Following introduction of the nucleic acid constructs, mice were kept in the absence of NTBC for selecting animals having complemented hepatocytes. In cotransfected cells, the transient expression of SB13 leads the stable integration of the expression cassette in the genome.

[0045] Analyses of mice after introduction of the nucleic acid constructs confirmed stable transcription of the inhibitory RNA from the nucleic acid construct. In detail, analysis of body weight of mice of FIG. 3 shows that the animals having received the control construct p/T-FAHIG (5) as well as the animals having received the control construct p/T-FAHIG-shCtr. (1), which expresses a non-specific RNA could not reconstitute liver function effectively but died.

[0046] Animals of those groups having received a nucleic acid construct containing an expression cassette for an inhibitory RNA which is specific for SEQ ID NO: 1, namely p/T-FAHIG-shMKK4.A (2,4) and p/T-FAHIG-shMKK4.B (3) could reconstitute liver function, as shown by the survival and restoration of body weights.

[0047] This result is further supported by FIG. 4 showing livers explanted at day 20 after administration of the nucleic acid construct, where livers are in the process of repopulation by hepatocytes which were co-transfected in vivo with a nucleic acid construct containing an expression cassette for FAH and GFP and including an expression cassette for inhibitory RNA specific for mRNA encoding MKK4 (p/T-FAHIG-shMKK4, both left-hand pictures), or including an expression cassette encoding a non-specific inhibitory RNA (p/T-FAHIG-shCtr, both right-hand pictures). The explanted livers of FIG. 4 show a faster increase of GFP fluorescence over time in vivo from animals co-transfected with the nucleic acid construct which includes the expression cassette encoding an inhibitory RNA specific for the mRNA encoding MKK4 compared to animals co-transfected with the nucleic acid construct which includes the expression cassette encoding an inhibitory RNA with no target.

[0048] The result from fluorescence is confirmed in this case in fully repopulated mouse lives by the immunospecific staining for MKK4 in the Western blot shown in FIG. 5 and by the immunofluorescence analyses for expression of MKK4 in the tissue samples of explanted mouse livers which are shown in FIG. 6.

[0049] In FIG. 5, shMKK4-224 denotes protein extracts from mouse livers repopulated with an expression cassette encoding an inhibitory RNA against MKK4 and shMKK4-3553 denotes protein extracts from mouse livers repopulated with an expression cassette encoding an independent inhibitory RNA against MKK4; tubulin served as a loading control and was detected by a specific antibody (.alpha.-tub), MKK4 was detected by an anti-MKK4 antibody (.alpha.-MKK4). In FIG. 6, FAHIG-shCtr denotes a nucleic acid construct containing the expression cassette for the complementing FAH and for GFP, including a non-specific inhibitory RNA (shCtr). shMKK4-A and shMKK4-B denote nucleic acid constructs containing expression cassettes for shRNA which specifically hybridize to the mRNA of MKK4.

[0050] Both analyses show that only the nucleic acid construct which includes an expression cassette encoding an inhibitory RNA specific for the mRNA encoding MKK4 results in a decrease of MKK4 expression in hepatocytes.

[0051] FIG. 7 shows Western blots for cyclin A and E of nuclear extracts from the mouse livers contacted with the nucleic acid construct expressing the shRNA hybridizing to MKK4 mRNA (shMKK4, +) and expressing the non-specific shRNA (shCtr, +), respectively, at 0, at 24 h, at 38 h, and at 48 h after partial hepatectomy, detected with .alpha.-cyclin A antibody (.alpha.-Cyc.A) and .alpha.-cyclin B antibody (.alpha.-CyC.B). This analysis shows that inactivation of MKK4, which is e.g. obtained by the expression of an inhibitory RNA hybridizing to the mRNA encoding MKK4, leads to an earlier entry of the cell cycle after partial hepatectomy.

[0052] FIG. 8 shows a Ki67 stain of livers of the experimental animals having received the nucleic acid construct expressing the inhibitory RNA specific for MKK4 mRNA (skMKK4) and of animals having received the construct expressing the non-specific shRNA (shCtr), respectively, at 0 h, 38 h, and 48 h following partial hepatectomy. The analyses show that the inactivation of MKK4, which in the example is obtained by presence of the shRNA which is specific for MKK4 mRNA and is expressed from the nucleic acid construct introduced into the hepatocytes results in an increase of hepatocyte proliferation in vivo.

[0053] FIG. 9 shows a quantification of the Ki67-positive cells from the analyses of FIG. 8. The increase in hepatocyte proliferation for the hepatocytes containing the shRNA inhibiting expression of MKK4 (p/T-FAHIG-shMKK4) is significant in comparison to the non-specific shRNA control (p/T-FAHIG-shCtr).

[0054] FIG. 10 shows TUNEL staining for identification of apoptotic cells in liver tissue from mice transfected by an integrating nucleic acid construct containing an expression cassette for non-specific shRNA (shCtr.), or an expression cassette for shRNA which specifically hybridizes to mRNA of MKK4 (shMKK4.224 or shMKK4.355, each expressing a mouse-specific siRNA hybridizing to the RNA of MKK4). Apoptosis was induced in vivo at 9 h prior to the analysis experimentally by injection of Jo2 antibody, which interacts with CD95 to induce fulminant liver failure. TUNEL staining reveals less apoptotic hepatocytes in the liver tissue expressing the MKK4-specific shRNA (shMKK4.224, shMKK4.355) than in controls (shCtr.). The upper row of pictures shows fluorescence micrographs of TUNEL analyses, the lower row shows bright field micrographs of H&E stained tissue samples.

[0055] the quantification of TUNEL analysis following induction of liver failure is shown in FIG. 11, demonstrating a significantly lower number of apoptotic hepatocytes in those liver tissues containing the shRNA (shMKK4.224 and shMKK4.3553) that hybridizes to mRNA of MKK4 when compared to the control with non-specific shRNA (shCtr.).

[0056] FIG. 12 shows the survival rate according to Kaplan Meier of mice transfected with the nucleic acid construct expressing the shRNA hybridizing to mRNA of MKK4 (shMKK4.224 and shMKK4.3553) and of control mice (shCtr.) after the experimental induction of liver failure. The result demonstrates that inactivation of MKK4, which inactivation in the example is obtained by expression of an inhibitory RNA (shRNA) from an expression of a nucleic acid construct, effectively protects hepatocytes in vivo against apoptosis.

Example 2

Inhibition of MKK4 In Vivo by Transcription of Inhibitory RNA From an Expression Cassette Encoding shRNA

[0057] For transient transfection of hepatocytes, a nucleic acid construct containing or consisting of an expression cassette encoding an inhibitory RNA which specifically hybridizes to the mRNA encoding MKK4, e.g. containing SEQ ID NO: 1 or SEQ ID NO: 2 (which are both specific for the human and the mouse mRNA of MKK4) was transiently introduced into hepatocytes. For transient transfection in vivo, the nuclei acid construct was formulated in liposomes and administered to the experimental animals. The liposome formulation contained the lipids 3-N-[(qmethoxypoly(ethylene glycol)2000)carbamoyl]-1,2-dimyristyloxy-propylamine)PEG-C-DMA), 1,2-dilinoleyloxy-N,N-dimethyl-3-aminopropane (DLinDMA), 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC) and cholesterol, in a 2:40:10:48 molar per cent ratio.

[0058] The effect of increasing proliferation of hepatocytes, protection against induction of apoptosis could be shown as laid out for the stable expression of the shRNA in Example 1, indicating that the effect was limited to the period in which the shRNA was present in the hepatocytes using the analytical methods as described in Example 1. This shows that MKK4 activity can effectively be inhibited or inactivated by transient expression of inhibitory RNA, e.g. shRNA or microRNA, from an expression cassette of a nuclei acid construct which does not integrate into the hepatocyte.

Example 3

Inhibition of MKK4 In Vivo by Inhibitory RNA Transfected Into Hepatocytes

[0059] Suitability of inhibitory RNA for use as a medicament could shown by transfecting the inhibitory RNA which specifically hybridizes to mRNA of MKK4 into liver tissue in vivo. Inhibitory RNA could be shRNA or microRNA, preferably formulated as liposomes or lipid nanoparticles. Generally, reduction or elimination of MKK4 could be obtained in at least a fraction of the liver tissue contacted by the formulation of the inhibitory RNA using the analytical methods as described in Example 1. This shows that inhibitory RNA specific for mRNA of MKK4 can be used as a medicament, especially for the treatment of impaired liver function.

Example 4

Inhibition of MKK4 In Vivo by SP600125, myricitine, Genistein, or PD98059 in Hepatocytes

[0060] In the alternative to inhibition of MKK4 activity in liver tissue by inhibitory RNA, SP600125, myricitine, Genistein, or PD98059 were used for inactivating MKK4 in the liver. Generally, SP600125, myricitine, Genistein, or PD98059 were administered to mice as a dosage efficient for in vivo inactivation of MKK4. Preferably, the dosage was efficient to inactivate at least 80%, more preferably at least 90 or 95% of mean in vivo MKK4 activity.

[0061] It could be found that the inactivation of MKK4 in the liver by administration of SP600125, myricitine, Genistein, or PD98059 as a medicament resulted in a significant increase in liver regeneration, an increase in proliferation, and in protection against induced apoptosis using the analytical methods as described in Example 1.

Example 5

Inhibition of MKK4 in Primary Hepatocytes Cultured In Vitro by Stable or Transient Transcription of Inhibitory RNA From an Expression Cassette Encoding shRNA

[0062] For in vitro transfection, cultured primary hepatocytes obtained from experimental animals were contacted by the nucleic acid construct as described in Example 1 or 2. Generally, the nucleic acid construct could be formulated as liposomes according to Example 2.

[0063] Generally, stable or transient expression of the inhibitory RNA could be obtained in the cultured hepatocytes, and reduction or elimination of MKK4 could be detected using the analytical methods as described in Example 1.

[0064] For experimental purposes, in the alternative to in vitro transfection of primary hepatocytes originating from an experimental animal, stably transfected hepatocytes expressing shRNA specific for MKK4 mRNA were isolated from the experimental mice generated according to Example 1. Analysis of cultured hepatocytes was by quantification of the incorporation of EdU by primary hepatocytes by flow cytometry. The result of cultured transfected hepatocytes after 3 days culture is shown in FIG. 13. The inset phase contrast micrographs and the relation of hepatocytes containing shRNA specific for mRNA of MKK4, generated by expression from the transfected expression cassette, show that cultured hepatocytes with inactivated MKK4 (FAHIG-shMKK4) show a drastically improved EdU incorporation as a marker for proliferation over controls (FAHIG-shCtr) without inhibition of MKK4 activity in culture.

[0065] Replating of the cultured hepatocytes in fresh culture medium shows the increased long-term survival of cultured hepatocytes in which MKK4 activity is essentially inhibited, e.g. by presence of inhibitory RNA (shMKK4) that specifically hybridizes to mRNA of MKK4, as shown in the micrographs of FIG. 14. Hepatocytes with inactivated MKK4 (shMKK4) can be cultured effectively at least to day 29 (d29), and can be cultured by trypsinizing and replating to fresh medium at day 15; right-hand micrographs show day 3 of cells replated after 15 days initial culture. In contrast, transfected cells with a non-specific shRNA (shCtr) show a lower long term survival in culture and no growth upon replating after 15 days initial culture.

[0066] These results show that the inactivation of MKK4 activity drastically increases long term survival and replating efficiency of cultured hepatocytes.

[0067] Generally, the generally known Eagles medium was used for hepatocyte cultures.

Example 16

Cultured Hepatocytes With Inactivated MKK4 Activity For Use as a Medicament For Liver Regeneration

[0068] Hepatocytes from a mouse representing a patient having a compatible or identical blood group, preferably hepatocytes that were immunologically compatible with a later recipient, e.g. a patient, preferably autologous hepatocytes, were cultured. MKK4 activity was inhibited as described in the above Examples, preferably by transfection of cultured hepatocytes with a nucleic acid construct containing an expression cassette for an inhibitory RNA hybridizing to the mRNA encoding MKK4, by transfection with an inhibitory RNA, preferably repeatedly, or by contacting with SP600125, myricitine, Genistein, or PD98059.

[0069] Cultured mouse hepatocytes which stably transfected with a nucleic acid construct expressing the complementing FAH and GFP (FAHIG) and an inhibitory RNA specific for the mRNA encoding MKK4 or a non-specific shRNA (Ctrl), respectively, were harvested by trypsinizing. These hepatocytes were suspended in a pharmaceutically acceptable carrier and transplanted into the spleen or liver of FAH -/- mice, which subsequently were kept without NTBC. The Kaplan Meier analysis of survival after intraspleenic transplantation of the cultured hepatocytes is shown in FIG. 15. In comparison to mice having received hepatocytes containing the non-specific shRNA (shRNA.Ctrl) that die at day 37-38 (vertical line), mice having received hepatocytes containing shRNA Mkk4 specific for the mRNA of MKK4 by expression from the expression cassette encoding the shRNA have a drastically increased survival.

[0070] The experimental FAH -/- mice that had repopulated livers with hepatocytes with an expression cassette for GFP, including the shRNA specific for the mRNA encoding MKK4 (shRNA.MKK4) were kept for 12 months following repopulation. Analyses of explanted livers in bright field photography (Bright), with GFP imaging (GFP) (left-hand pictures of FIG. 16) and anti-FAH immunofluorescence and H&E staining of liver section (right-hand pictures of FIG. 16) show no tumor development with stable intrahepatic expression of GFP and of the shRNA specifically inactivating MKK4. These data emphasize that MKK4 inhibition can be used to increase regeneration without triggering tumor growth.

[0071] Example 7

Cultivated Hepatocytes With Inactivated MKK4 Activity For Use as a Device For Extracorporal Blood Purification

[0072] Cultured hepatocytes obtained as described above, preferably by cultivating primary hepatocytes which were stable transfected with a nucleic acid construct expressing an shRNA specific for the mRNA encoding MKK4 were grown on a carrier substrate, e.g. a polymer carrier. The cultured hepatocytes adhering to the carrier substrate were arranged in a container which was perfused with blood withdrawn from a patient, exemplified by a moose or rat. Blood exiting the container could immediately be returned into the patient.

[0073] In initial experiments, it could be shown that hepatocytes which are genetically manipulated to stably express an shRNA inactivating the mRNA encoding MKK4 are stable when grown on a carrier substrate, and that these cultures hepatocytes could be used as a blood purification device.

Example 8

Inactivation of MKK4 in In Vitro Analyses

[0074] The inhibitory effect of compounds against MKK4 analysed in an in vitro assay using purified MKK4 protein, e.g. obtained from a cell line that was genetically manipulated to over-express MKK4 from an expression cassette containing the nucleotide sequence SEQ ID NO: 1204 as a coding sequence and affinity purification using e.g. an antibody directed against MKK4 protein.

[0075] In the assay, purified active MKK4 protein was incubated with its substrate JNK1a1 and .sup.32P-labelled gATP (5 .mu.Ci, approx. 10 .mu.M), without additional active compound, with the small inhibitory compound, or with Genistein as a positive control. For the assay, kinase assay buffer (20 mM HEPES pH 7.5; 10 mM MgCl.sub.2; 1 mg/ml BSA; 1 mM N.sub.3VO.sub.4; 1 mM DDT) was used. An inhibitory effect of the small inhibitory compound (final concentration 50 .mu.M) was detected as a reduction of the phosphorylation activity of MKK4 protein on its substrate JNK1a1 by measuring the amount of radioactive (.sup.32 P) phosphate in JNK1a1. Phosphorylation of JNK1a1 was measured in the presence of 2 ml scintillation cocktail per sample by using a scintillation counter (Wallac, liquid Scintillation Counter). In this assay, Genistein gave an inhibition to approx. 80% activity compared to the assay without additional active compound.

TABLE-US-00001 TABLE 1 small inhibitory compounds assayed for inhibitory activity against MKK4: Inhibition, relative activity of MKK4 compared to control (without additional compound) name Structure (%) ZM 336372; 3-(Dimethylamino)- N-[3-[(4- hydroxybenzoyl)- amino]-4- methyl- phenyl]benzamide ##STR00001## 54.2 BAS00525963; 2-hydroxy-1- methyl-4-oxo-N- pyridin-4- ylquinoline-3- carboxamide ##STR00002## 72.6 BAS00697444; 2-(1H-indazol-5- yliminomethyl)-6- nitrophenolate ##STR00003## 79.0 SYN22174524; 5-[2-(3,5-dimethyl- 1H-pyrazol-4- yl)ethyl]-7-oxo-N- phenyl-1H- pyrazolo[1,5- a]pyrimidine-3- carboxamide ##STR00004## 47.8 SYN22174787; 5-[2-(3,5-dimethyl- 1H-pyrazol-4- yl)ethyl]-3-(4- fluorophenyl)-1H- pyrazolo[1,5- a]pyrimidin-7-one ##STR00005## 41.5 SYN22175977; 5-[2-(3,5-dimethyl- 1H-pyrazol-4- yl)ethyl]-3-(4- methylphenyl)-1H- pyrazolo[1,5- a]pyrimidin-7-one ##STR00006## 55.5 SYN22176267; 3-(4-chlorophenyl)- 5-[2-(3,5-dimethyl- 1H-pyrazol-4- y)ethyl]-2- (methoxymethyl)- 1H-pyrazolo[1,5- a]pyrimidin-7-one ##STR00007## 59.1 SYN22176367; 5-[2-(3,5-dimethyl- 1H-pyrazol-4- yl)ethyl]-2- (methoxymethyl)-3- (4-methylphenyl)- 1H-yrazolo[1,5- a]pyrimidin-7-one ##STR00008## 49.9 SYN22176842; 5-[2-(3,5-dimethyl- 1H-pyrazol-4- yl)ethyl]-2-(3- methoxyphenyl)-3- methyl- pyrazolo[5,1- b]pyrimidin-7-ol ##STR00009## 54.9 SYN22176990; 5-[2-(3,5-dimethyl- 1H-pyrazol-4- yl)ethyl]-2-(2- methoxyphenyl)-3- methyl- pyrazolo[5,1- b]pyrimidin-7-ol ##STR00010## 58.2 SYN22177890; 3-(4-chlorophenyl)- 5-[2-(3,5-dimethyl- 1H-pyrazol-4- yl)ethyl]-2-methyl- 1H-pyrazolo[1,5- a]pyrimidin-7-one ##STR00011## 56.3 BAS00896568; 5-amino-3-[(Z)-1- cyano-2-[3-[(4- methoxy-6- piperidin-1-yl-1,3,5- triazin-2- yl)oxy]phenyl]eth- enyl]-1-(2- hydroxyethyl)py- razole-4-carbonitrile ##STR00012## 58.4 BAS00697462; 2-(1H-indazol-5- yliminomethyl)-6- methoxy-4- nitrophenolate ##STR00013## 71.1 BAS00368055; 7-oxobenzo[e]- perimidine-4- carboxylic acid ##STR00014## 66.2 IUPAC Name: 1- phenyl-2-[[4- phenyl-5-[(5- phenyltetrazol-2- yl)methyl]-1,2,4- triazol-3- yl]sulfanyl]ethanone ##STR00015## IUPAC Name: 2- [[5-[(2,4-dimethyl- anilino)methyl]-4- (furan-2-ylmethyl)- 1,2,4-triazol-3- yl]sulfanylmethyl]- 1H-quinazolin-4- one ##STR00016## N-(2-furylmethyl)- N-[1- (isopentylcarbamoyl) ethyl]-5- (morpholinomethyl)- furan-2- carboxamide ##STR00017## IUPAC Name: 4-N- benzyl-1-N-[2-(3,4- dimethoxyphenyl)- ethyl]-4-N- ethylbenzene-1,4- disulfonamide ##STR00018## IPUAC Name: 3-[2- (2,5- dimethoxyphenyl)- 2- oxoethyl]sulfanyl- 6-methyl-2H-1,2,4- triazin-5-one ##STR00019## IUPAC Name: 2-[4- (4-methylbenzoyl)- piperidin-1- yl]sulfonylbenzoate ##STR00020## IUPAC Name: 2-[4- [(2,4-dioxo-1,3- thiazolidin-5- ylidene)methyl]-2- methoxyphenoxy]- acetic acid ##STR00021## Popular Name: N- (6-ethoxy-1,3- benzothiazol-2-yl)- 2-[[2-(p-tolyl)-9H- purin-6- yl]sulfanyl]acetamide ##STR00022## 2-[4-(4-methoxy- phenyl)-piperazin- 1-yl]-N-(3- morpholino- sulfonyl-phenyl)- acetamide ##STR00023## Popular Name: 5- [[4-[(2,4,6- trioxohexa- hydropyrimidin-5- ylidene)methyl]- phenoxy]methyl]- furan-2-carboxylic ##STR00024## IUPAC Name: 3- (benzimidazol-1- yl)-N-[(2R)-1-[3- (3,4- difluorophenyl)-6- oxopyridazin-1- yl]butan-2- yl]propanamide ##STR00025## IUPAC Name: 2- methyl-3-(pyridin- 3-ylmethyl- amino)benzoate ##STR00026## IUPAC Name: N- [2-[[4-amino-6- (dimethylamino)- 1,3,5-triazin-2- yl]oxy]ethyl]-2-(4- chloro-2- methylphenoxy)acet- amide ##STR00027## IUPAC Name: [3- ethoxy-4-(thiophen- 2- ylmethoxy)phenyl] methyl-(2- morpholin-4-ium-4- ylethyl)azanium ##STR00028## IUPAC Name: 2-[4- (2- hydroxyethyl)pipera- zin-2-yl]-N-(2- pyrrolidin-1- ylsulfonylethyl)pyri- dine-3-carboxamide ##STR00029## IUPAC Name: 1-[[2-(furan-2-yl)- pyrrolo[2,3-b]pyridin-3-yl]methyl- methylamino]-3-(4- methoxyphenoxy)propan-2-ol ##STR00030## IUPAC Name: N- ethyl-3-[2-(4- methoxyphenoxy)eth- oxy]-N- (pyrazolo[1,5- a]pyrimidin-3- ylmethyl)aniline ##STR00031## IUPAC Name: N- ethyl-3-[2-(4- fluorophenoxy)ethoxy]- N-[(2- methylpyrimidin-5- yl)methyl]aniline ##STR00032## IUPAC Name: 2- methoxy-5- morpholin-4- ylbenzoate ##STR00033## IUPAC Name: (1R,2S,3R)-3-(2- aminobenzoyl)-3- methyl-2-N-[(5- methyl-1,2,4- oxadiazol-3- yl)methyl]-1-N- (pyridin-4- ylmethyl)cyclo- propane-1,2- dicarboxamide ##STR00034## IUPAC Name: (2S,3S)-2,3- bis(ethoxycarbonyl) butanedioate ##STR00035## IUPAC Name: diethyl 2-[(1,4- diethoxy-1,4- dioxobut-2-en-2- yl)amino]but-2- enedioate ##STR00036## IUPAC Name: (2S,3S)-2,3- bis(ethoxycarbonyl) butanedioate ##STR00037## IUPAC Name: diethyl 2-[(1,4- diethoxy-1,4- dioxobut-2-en-2- yl)amino]but-2- enedioate ##STR00038## IUPAC Name: 1-ethyl-2-hydroxy-N- (4-hydroxyphenyl)-4- oxoquinoline-3- carboxamide ##STR00039## IUPAC Name: 5- (phenylcarbamoyl- oxy)pentyl N- phenylcarbamate ##STR00040## Popular Name: N- [(5-acetamido-2- methoxy- phenyl)methyl]-2- morpholino- acetamide ##STR00041## IUPAC Name: 4- [4,6-bis(3- carboxypropyl)- 1,3,5-trioxan-2- yl]butanoic acid ##STR00042## IUPAC Name: methyl4- [(4-oxo-2- sulfanylidene-1,3- thiazolidin-5- ylidene)meth- yl]benzoate ##STR00043## IUPAC Name: 2- (3-methylanilino)- N-[(3- nitrophenyl)methyl- ideneamino]acetamide ##STR00044## IUPAC Name: [(2R)-2-[3- [bis[3- (dimethylazaniumyl) propyl]amino]pro- panoyloxy]-3- (dimethylamino)pro- pyl]- dimethylazanium ##STR00045## IUPAC Name: 2-hydroxy-4-oxo-N- pyridin-4-yl-1H-quinoline-3- carboxamide ##STR00046## IUPAC Name: 1-ethyl-2-hydroxy-4-oxo- N-pyridin-4-ylquinoline-3-carboxamide ##STR00047## IUPAC Name: 2,3- bis[2-(2- nitrophenoxy)ethoxy]- 1,4-dioxane ##STR00048## 4-hydroxy-2-oxo- N-(4- pyridinylmethyl)- 1,2-dihydro-3- quinoline carboxamide ##STR00049## IUPAC Name: 7- oxobenzo[e]perimi- dine-4-carboxylic acid ##STR00050## IUPAC Name: 1,3- dioxobenzo[de]iso- quinoline-6- carboxylic acid ##STR00051## IUPAC Name: diethyl(2S)- 2-[[3-[[(2S)-1,5- diethoxy-1,5- dioxopentan-2- yl]amino]-3- oxopropanoyl]amino] pentanedioate ##STR00052## IUPAC Name: diethyl2- [[2-acetamido-3- (4- phenylmethoxyphe- nyl)propanyl]amino] pentanedioate ##STR00053## IUPAC Name: 3- nitor-N[(E)-[3- [(E)-[(3- nitrophenyl)hydrazinyl- idene]methyl]phe- nyl]methylidene amino]aniline ##STR00054## IUPAC Name: (4- methoxyphenyl)meth- ylN-[[4-[2-(3,4- dimethoxyphenyl)eth- ylamino]-4- oxobutan-2- ylidene]amino]carb- ##STR00055## amate IUPAC Name: 3- amino-1,5- dihydropyrimido[5,4- b]indole-2,4- dione ##STR00056## IUPAC Name: 1- [2-(2- fluorophenoxy)eth- yl]-3-[6-[2-(2- fluorophenoxy)eth- ylcarbamoylamino] hexyl]urea ##STR00057## IUPAC Name: methyl4- [[[2-[2-[[4- [hydroxy(methoxy) methyl]phenyl]meth- ylidene]hydrazinyl]- 2- oxoethoxy]acetyl]hydra- zinylidene]meth- yl]benzoate ##STR00058## IUPAC Name: N- [2-(3,4- dimethoxyphenyl)eth- yl]-2-quinolin-8- ylsulfamoylacetamide ##STR00059## IUPAC Name: (2S,3S)- 2,3-bis(4- butoxyphenoxy)- 1,4-dioxane ##STR00060## IUPAC Name: 2-hydroxy- 1-methyl-4-oxo-N- pyridin-4-ylquinoline-3-carboxamide ##STR00061## IUPAC Name: quinoline- 2,4-dicarboxylic acid ##STR00062## IUPAC Name: 2- [(5Z)-5-[(3- hydroxyphenyl)meth- ylidene]-4-oxo-2- sulfanylidene-1,3- thiazolidin-3- yl]propanoic acid ##STR00063## IUPAC Name: diethyl2- acetamido-2-[[5- amino-2-(2-ethoxy- 2- oxoethoxy)phenyl] methyl]propanedioate ##STR00064## IUPAC Name: 4- [2-[2-[2-[(4-amino- 1,2,5-oxadiazol-3- y)oxy]ethoxy]ethoxy] ethoxy]-1,2,5- oxadiazol-3-amine ##STR00065## IUPAC Name: (1R,2S,3S,4S)- 2-(thiophen-2- ylmethylcarbamoyl) bicyclo[2.2.1]hept- 5-ene-3- carboxylate ##STR00066## IUPAC Name: 3- [4-[2-[(4,4- dimethyl-2,6- dioxocyclohexylidene) methylamino]eth- yl]piperazin-1- yl]-1- phenylpyrrolidine- 2,5-dione ##STR00067## IUPAC Name: methyl4- [N-[2-(N-(4- methoxy-4- oxobutanoyl)anilino) ethyl]anilino]-4- oxobutanoate ##STR00068## IUPAC Name: 7- propan-2-ylidene- 2-(pyridin-3- ylmethylcarbamoyl) bicyclo[2.2.1]hept- 5-ene-3- carboxylic acid ##STR00069## 1-[4-[2-hydroxy- 3-(2- pyridylmethylamino) propoxy]phenoxy]- 3-(2- pyridylmethylamino) propan-2-ol ##STR00070## IUPAC Name: 3- [5-[(4- hydroxyphenyl)meth- ylidene]-4-oxo-2- sulfanylidene-1,3- thiazolidin-3- yl]propanoic acid ##STR00071## 2-(1-benzothiazol- 2 - ylaminoiminoethyl- azo)benzoic ##STR00072## IUPAC Name: 2- [(3-acetylphenyl)- carbamoyl]bicycle- [2.2.1]hept-5-ene- 3-carboxylate ##STR00073## IUPAC Name: 2- (1H-indazol-5- yliminomethyl)-6- nitrophenolate ##STR00074## IUPAC Name: 2- bromo-6-[(1H- indazol-5- ylamino)- methylidene]-4- nitrocyclohexa-2,4- dien-1-one ##STR00075## IUPAC Name: 2- (1H-indazol-5- yliminomethyl)-6- methoxy-4- nitrophenolate ##STR00076## N-{2-[2-(1- methyl-4- piperidinylidene)- hydrazino]-2- oxoethyl}-N-(3- nitrophenyl)benzene- sulfonamide (non- preferred name) ##STR00077##

IUPAC Name: 4- [5-(naphthalen-1- ylmethylidene)-4- oxo-2- sulfanylidene-1,3- thiazolidin-3- yl]butanoate ##STR00078## IUPAC Name: 5- amino-3-[(Z)-1- cyano-2-[3-[(4- methoxy-6- piperidin-1-yl- 1,3,5-triazin-2- yl)oxy]phenyl]ethe- nyl]-1-(2-hydroxy- ethyl)pyrazole- 4-carbonitrile ##STR00079## IUPAC Name: 8- [2-methoxy-4-[(1- oxo- [1,3]thiazolo[3,2- a]benzimidazol-2- ylidene)meth- yl]phenoxy]-1,3,7- trimethylpurine- 2,6-dione ##STR00080## IUPAC Name: 2- [2-[2-(4- methylphenyl)sulfo- nylethoxy]ethoxy]eth- yl4- methylbenzenesulf- onate ##STR00081## IUPAC Name: (2S)-3- acetyl-4-hydroxy- 1-(4- hydroxyphenyl)-2- phenyl-2H-pyrrol- 5-one ##STR00082## IUPAC Name: bis[2-(3,4- dimethylphenyl)-2- oxoethyl] cyclohexane-1,2- dicarboxylate ##STR00083## IUPAC Name: 8- (butoxymethyl)-3- [2-[[5-(2- chlorophenyl)-1H- 1,2,4-triazol-3- yl]sulfanyl]acetyl]- 3-methyl-2,7- dioxaspiro[4.4]non- ane-1,6-dione ##STR00084## IUPAC Name: 2- (naphthalen-2- ylsulfonyl- amino)butanoic acid ##STR00085## 1-(3,5- dimethoxyphenyl)- N-[(2- nitrophenyl)methyl] methanamine ##STR00086## IUPAC Name: 5- [(2- carboxylatophenyl) sulfamoyl]-2-(3- carboxylatopropyl- amino)benzoate ##STR00087## IUPAC Name: 2- (7H-purin-6- ylazaniumyl)acetate ##STR00088## IUPAC Name: [2- (4-bromophenyl)- 2-oxoethyl]6-(5- methyl-2-oxo-1,3- dihydroimidazol-4- yl)-6-oxohexanoate ##STR00089## 3-(2,3-dihydro-1H- indol-1- ylcarbonyl)-1,2,2- trimethylcyclo- pentanecarboxylic acid ##STR00090## IUPAC Name: benzyl-N- [2-[2-[(4-methoxy- 3-nitrophenyl)- methylidene]- hydrazinyl]-2- oxethyl]-N- methylcarbamate ##STR00091## IUPAC Name: methyl4- [[2-[2-[2-[(4- methoxy-4- oxobutyl)amino]-2- oxoethoxy]phenoxy] acetyl]amino]butanoate ##STR00092## IUPAC Name: [2- acetyloxy-4-[2-[5- (ethoxymethyl)-4- imino-2- methylpyrimidin-1- yl]acetyl]phenyl] acetate ##STR00093## IUPAC Name: (4- chloro-2- methylphenyl)meth- ylN-[2-[[4- (dimethylamino)-6- [methoxy(meth- yl)amino]-1,3,5- triazin-2- yl]oxy]ethyl]carba- mate ##STR00094## 1-[4-[2-hydroxy-3- (2-nitrophenoxy)- propyl]piperazin-1- yl]-3-(2- nitrophenoxy)- propan-2-ol ##STR00095## IUPAC Name: 2- [(5R)-3-(4- hydroxyphenyl)- 2,4-dioxo-1,3- thiazolidin-5- yl]acetate ##STR00096## IUPAC Name: 2- [2-(2,4- dihydroxyphenyl)- 2- oxoethyl]sulfanyl- 4-hydroxy-1H- pyrimidin-6-one ##STR00097## IUPAC Name: 4- hydroxy-2-[2-(1H- indol-3-yl)-2- oxoethyl]sulfanyl- 1H-pyrimidin-6- one ##STR00098## IUPAC Name: 3- (3-anilino-2- hydroxypropyl)-1- [[3-(3-anilino-2- hydroxypropyl)- 5,5-dimethyl-2,4- dioxoimidazolidin- 1-yl]methyl]-5,5- dimethylimidazolidine- 2,4-dione ##STR00099## 1-(2-furylmethyl)- 4-(3-nitrobenzyl)- piperazine ##STR00100## IUPAC Name: 2- nitro-6-[(5-pyridin- 4-yl-1,3,4- thiadiazol-2- yl)carbamoyl]benzoic acid ##STR00101## IUPAC Name: [2- [[[2-(4- phenylphenoxy)ace- tyl]hydrazinylidene] methyl]phenyl] acetate ##STR00102## 2-((4'-HYDROXY- NAPHTHYL)- AZO)BENZOIC ACID ##STR00103## 8-hydroxy-5,6- dihydro-4H-11- oxa-6a- azabenzo[de]anthra- cene-7,10-dione ##STR00104## IUPAC Name: 2- (pyridin-3- ylmethylcarbamoyl) bicyclo[2.2.1]hept- 5-ene-3- carboxylate ##STR00105## 4-Ethyl-5-(4- hydroxyphenyl)- 4H-[1,2,4]triazol- 3-ylsulfanyl]-acetic acid ##STR00106## IUPAC Name: 5- [[4-(benzylamino)- 3- nitrophenyl]sulfonyl- ylamino]benzene- 1,3-dicarboxylate ##STR00107## IUPAC Name: 4- [4-(4-carboxylato- phenoxy)phenyl]- sulfonylphthalate ##STR00108## N-[(2,4- dihydroxyphenyl)- methyleneamino]- 2-[(8-methoxy-2- methyl-4- quinolyl)- sulfanyl]acetamide ##STR00109## IUPAC Name: 1- [2-[2-[2-[2-(2- acetyl- phenoxy)ethoxy]- ethoxy]ethoxy]- phenyl)ethanone ##STR00110## IUPAC Name: [2- [4-(4-chloro-2- nitro- phenoxy)phenyl]- 2-oxoethyl] 2- benzamidoacetate ##STR00111## IUPAC Name: phenacyl 3- [phenacyl- (phenacylamino)- amino]benzoate ##STR00112## IUPAC Name: 1- (4-amino-1,2,5- oxadiazol-3-yl)-5- (1H-benzimidazol- 2- ylsulfanylmethyl)- N-[1-(5-nitrofuran- 2- yl)ethylideneamino]- triazole-4- carboxamide ##STR00113## IUPAC Name: 2- benzamido-N-[1- (furan-2- ylmethylamino)-1- oxopropan-2- yl]benzamide ##STR00114## IUPAC Name: 2- benzamido-N-[1- (3-imidazol-1- ylpropylamino)-1- oxo-3- phenylpropan-2- yl]benzamide ##STR00115## IUPAC Name: ethyl2-[[2- [2-(2,3-dioxoindol- 1- yl)acetyl]oxyacetyl]- amino]-4-methyl- 1,3-thiazole-5- carboxylate ##STR00116## IUPAC Name: ethyl5-[[5- ethoxycarbonyl-3- (2-methoxy-2- oxoethyl)-4- methyl-1H-pyrrol- 2-yl]methyl]-4-(3- methoxy-3- oxopropyl)-3- methyl-1H-pyrrole- 2-carboxylate ##STR00117## IUPAC Name: ethyl2-[[2-(1H- benzimidazol-2- ylsulfanyl)acetyl]- amino]-6-methyl- 5,7-dihydro-4H- thieno[2,3-c]- pyridine-3- carboxylate ##STR00118## keto(3-pyridyl- methylcarbamoyl)- BLAHolate ##STR00119## keto(4- pyridylmethyl- carbamoyl)BLAH- olate ##STR00120## hydroxy-oxo-N-(4- pyridyl)BLAH- carboxamide ##STR00121## IUPAC Name: 3- [[(5R)-2,4-dioxo- 1,3-thiazolidin-5- yl]amino]benzoate ##STR00122## methyl N-acetyl-5- (1,3-dioxo-1,3- dihydro-2H- isoindol-2-yl)-2- (2H-tetrazol-5- yl)norvalinate ##STR00123## IUPAC Name: 3- [(2,3-dioxo-1,4- dihydroquinoxalin- 6- yl)sulfonyl]propan- oate ##STR00124## IUPAC Name: N- [2-(3,4- dimethoxyphenyl)eth- yl]-2-[[5-[(4,6- dimethylpyrimidin- 2-yl)sufanyl- methyl]-1,3,4- oxadiazol-2-yl]- sulfanyl]acetamide ##STR00125## IUPAC Name: (2S)-1- (2,1,3- benzothiadiazol-4- ylsulfonyl)piperidine- 2-carboxylic acid ##STR00126## benzyl(veratryl)- BLAH ##STR00127## IUPAC Name: 2- [1-(1,3- benzodioxol-5-yl)- 2,5- dioxopyrrolidin-3- yl]sulfanylpyridine- 3-carboxylate ##STR00128## IUPAC Name: 2- [4-(5-acetyl-1- hydroxy-4- methylimidazol-2- yl)-2-ethoxy- phenoxy]-N-(3- methylphenyl)- acetamide ##STR00129## (3-chlorophenyl)- keto-BLAH- carboxylate ##STR00130## 1-naphthyl-oxo- BLAHcarboxylic acid ##STR00131## IUPAC Name: 2- (3,4- dimethoxyphenyl)- 1-[4-(2- fluorophenyl)- piperazin-1- yl]ethanone ##STR00132## IUPAC Name: 4- (4-ethoxyphenyl)- 5-pyridin-4-yl- 1,2,4-triazole-3- thiolate ##STR00133## IUPAC Name: 4- (3-methylphenyl)- 5-pyridin-4-yl- 1,2,4-triazole-3- thiolate ##STR00134## IUPAC Name: ethyl 2-(2-benzyl- sulfonylbenzimid- azol-1-yl)acetate ##STR00135## IUPAC Name: 2- [(3S)-1-(1,3- benzodioxol-5-yl)- 2,5- dioxopyrrolidin-3- yl]sulfanyl- benzoate ##STR00136## Popular Name: 1- [3-(3-methoxy- phenoxy)propyl]-4- [(4-methylphenyl)- sulfonyl]piperazine ##STR00137## IUPAC Name: 3- (pyridin-3- ylmethyl- amino)benzoic acid ##STR00138## 2-(4-hydroxy- phenyl)quinoline- 4-carboxylic acid ##STR00139## IUPAC Name: 6- (2-pyridin-4- ylethylcarbamoyl)cyclo- hex-3-ene-1- carboxylate ##STR00140## IUPAC Name: 2- [(3S)-1-(4- hydroxyphenyl)- 2,5- dioxopyrrolidin-3- yl]sulfanylbenzoate ##STR00141## IUPAC Name: 4- (4- methoxyphenyl)-5- pyridin-4-yl-1,2,4- triazole-3-thiolate ##STR00142## IUPAC Name: ethyl5-[(2R)-3- (3,5- dimethylpyrazol-1- yl)-2-hydroxy- propoxy]-1,2- dimethylindole-3- carboxylate ##STR00143## IUPAC Name: 1- naphthalen-2-yl- sulfonylpyrrolidine- 2-carboxylic acid ##STR00144## IUPAC Name: (2S)-2- [(2,3-dioxo-1,4- dihydroquinoxalin- 6-yl)sulfonyl- amino]propanoate ##STR00145## IUPAC Name: (2R)-3- acetyl-4-hydroxy- 1-[2-(1H-indol-3- yl)ethyl]-2-pyridin- 2-yl-2H-pyrrol-5- one ##STR00146## .2.1.0%1,5&]dec- 8-ene-6-carboxylic acid ##STR00147## IUPAC Name: (3S)-3-(1H- indol-3-yl)-3- pyridin-4- ylpropanoic acid ##STR00148## IUPAC Name: 5- methyl-2-pyridin- 4-yl-1H- [1,2,4]triazolo[1,5- a]pyrimidin-7-one ##STR00149## IUPAC Name: (2S)-1-(1- methyl-2- oxobenzo[cd]indol- 6- yl)sulfonylpyrrolidine- 2-carboxylic acid ##STR00150## IUPAC Name: [2- [4-(furan-2- carbonyloxy)phenyl]- 2-oxoethyl]1- (furan-2-ylmethyl)- 5-oxopyrrolidine- 3-carboxylate ##STR00151## IUPAC Name: 4- [2-[5-(4- methoxyphenyl)- 1H-pyrazol-4- yl]ethenyl]-6- (trifluoromethyl)- 1H-pyrimidin-2- one ##STR00152## IUPAC Name: 2-hydroxy-5-[[(E)- (3-methyl-5-oxo-1H- pyrazol-4-ylidene)- methyl]amino]- benzoate ##STR00153## IUPAC Name: 3- oxo-2-(pyridin-4- ylmethyl)-1H- isoindole-4- carboxylic acid ##STR00154## 8-hydroxy- [1]benzofuro[3,2- b]quinoline-11- carboxylic acid ##STR00155## IUPAC Name: 5- [[3-methoxy-4- (thiophen-2- ylmethoxy)phenyl] methylamino]-2- morpholin-4- ylbenzoate ##STR00156## oxylic acid ##STR00157## (3R)-4-keto-3- morpholin-4-ium- 4-yl-4-(2-phenoxy ethoxy)butyrate ##STR00158## (3R)-4-keto-3- morpholin-4-ium- 4-yl-4-[[(2S)- tetrahydrofuran-2- yl]methoxy]butyrate ##STR00159## 4-oxo-4-[2-[4-(p- tolylsulfonyl)- piperazin-1- yl]ethoxy]butanoic acid ##STR00160## IUPAC Name: 4- (3-chloro-4- fluoropehnyl)-3- pyridin-4-yl-1H- 1,2,4-triazole-5- thione ##STR00161## 3-[3-(4-pyridyl)-5- thioxo-1H-1,2,4- triazol-4- yl]benzoic ##STR00162##

IUPAC Name: 1-(3-phenyl- adamantane-1- carbonyl)pyrrolidine- 2-carboxylic acid ##STR00163## IUPAC Name: 4-(2,3-dihydro-1,4- benzodioxin-6-yl)- 3-(3- hydroxyphenyl)- 1H-1,2,4-triazole- 5-thione ##STR00164## (dimethylBLAHyl)- methyl ##STR00165## IUPAC Name: N- [1-(3-imidazol-1- ylpropylamino)-3- methyl-1- oxobutan-2-yl]-2- [(4-methoxy- benzoyl)amino]benz- amide ##STR00166## IUPAC Name: 1-ethyl-3-methyl- 2-oxoquinoxaline- 6-carboxylate ##STR00167## IUPAC Name: 3-(4-oxo-2H- pyrazolo[3,4- d]pyrimidin-1- yl)propanoate ##STR00168## 3-(benzotriazol-1- yl)-1-[(3R)-3-[4- (3-methylisoxazol- 5-yl)-2H-pyrazol- 3-yl]-1-piperidyl]- propan-1-one ##STR00169## IUPAC Name: N-[2-(5-oxo-4- phenyltetrazol-2- yl)ethyl]-2-(4-oxo- 3H-phthalazin-1- yl)acetamide ##STR00170## IUPAC Name: ethyl4-[[4- (7-amino-2- methyl- pyrazolo[1,5- a]pyrimidin-5- yl)piperidin-1- yl]methyl]-3,5- dimethyl-1H- pyrrole-2- carboxylate ##STR00171## IUPAC Name: [4- (4-methyl-5- pyrimidin-4-yl-1,3- thiazol-2- yl)piperidin-1-yl]- (1H-1,2,4-triazol- 5-yl)methanone ##STR00172## IUPAC Name: 3- methyl-1-phenyl-5- [(2-pyrrolidin-1- ylsulfonylethyl- amino)methyl]-2H- pyrazolo[3,4- b]pyridin-6-one ##STR00173## 1-[2-(4-methoxy- phenyl)pyrimidin- 5-yl]-N-methyl-N- (4,5,6,7-tetrahydro- 1H-indazol-3- ylmethyl)methan- amine ##STR00174## IUPAC Name: N- [[2-(4- methoxy- phenyl)pyrimidin-5- yl]methyl]-N- methyl-1-pyridin- 2-ylpropan-2- amine ##STR00175## IUPAC Name: N- methyl-N-(2- phenoxyethyl)-2- quinazolin-4- yloxyacetamide ##STR00176## IUPAC Name: N- [2-[4-(4- fluorophenyl)-4- hydroxypiperidin- 1-yl]ethyl]-2-[(5- methyl-1,3,4- oxadiazol-2- yl)sulfanyl]- acetamide ##STR00177## IUPAC Name: 5- (2-ethoxypyridin- 3-yl)-3-[2-(2- propan-2- ylpyrrolo[2,3- b]pyridin-1- yl)ethyl]-1,2,4- oxadiazole ##STR00178## IUPAC Name: N- [1-(3,4-dihydro- 2H-1,5- benzodioxepin-7- yl)-2- methylpropyl]-6- (2-hydroxyethyl)- pyrazolo[1,5- a]pyrimidine-3- carboxamide ##STR00179## IUPAC Name: N- [2-(1-methyl- benzimidazol-2- yl)ethyl]-2-[2-(3- methyl-1,2,4- oxadiazol-5- yl)phenoxy]- acetamide ##STR00180## 2-amino-5-[2-[4- [3-(2,3-dimethyl- phenoxy)propyl]- piperazin-1-yl]-2- oxo-ethyl]-6- methyl-3H- pyrimidin-4- ##STR00181## IUPAC Name: N- [1-(3,5-dimethyl- pyrazol-1- yl)propan-2-yl]-1- (1,5- dimethylpyrazol-4- yl)sulfonylpiperidine- 4-carboxamide ##STR00182## IUPAC Name: 4- [(3,5-dimethyl- pyrazol-1- yl)methyl]-N-[2- (4-fluorophenoxy)- phenyl]-5-methyl- 1,2-oxazole-3- carboxamide ##STR00183## IUPAC Name: 2-(3-methyl-2,6- dioxopurin-7-yl)- N-[1-(7-methyl- 1H-indol-3- yl)propan-2- yl]acetamide ##STR00184## IUPAC Name: 7-bicyclo[4.1.0]- heptanyl-[4-[3-(2- methoxyphenoxy)- propyl]piperazin-1- yl]methanone ##STR00185## IUPAC Name: 5- [2-(3,5-dimethyl- 1H-pyrazol-4- yl)ethyl]-7-oxo-N- phenyl-1H- pyrazolo[1,5- a]pyrimidine-3- carboxamide ##STR00186## IUPAC Name: 5-[2-(3,5-dimethyl- 1H-pyrazol-4-yl)- ethyl]-3-(4-fluoro- phenyl)-1H-pyrazolo- [1,5-a]pyrimidin- 7-one ##STR00187## IUPAC Name: 5-[2-(3,5-dimethyl- 1H-pyrazol-4- yl)ethyl]-3-(4- methylphenyl)-1H- pyrazolo[1,5-a]- pyrimidin-7-one ##STR00188## IUPAC Name: 5-[2-(3,5-dimethyl- 1H-pyrazol-4-yl)- ethyl]-2-(methoxy- methyl)-3-phenyl- 1H-pyrazolo [1,5-a]pyrimidin-7- one ##STR00189## IUPAC Name: 3-(4-chlorophenyl)-5- [2-(3,5-dimethyl-1H- pyrazol-4-yl)ethyl]- 2-(methoxymethyl)- 1H-pyrazolo[1,5-a]- pyrimidin-7-one ##STR00190## IUPAC Name: 5-[2-(3,5-dimethyl- 1H-pyrazol- 4-yl)ethyl]-2- (methoxymethyl)- 3-(4-methylphenyl)- 1H-pyrazolo [1,5-a]pyrimidin-7- one ##STR00191## 2-(3,4-dimethoxy- phenyl)-5-[2-(3,5- dimethyl-1H- pyrazol-4- yl)ethyl]pyrazolo- [5,1-b]pyrimidin-7- ol ##STR00192## 5-[2-(3,5-dimethyl- 1H-pyrazol-4- yl)ethyl]-2-(3- methoxyphenyl)-3- methyl- pyrazolo[5,1- b]pyrimidin-7-ol ##STR00193## 5-[2-(3,5-dimethyl- 1H-pyrazol-4- yl)ethyl]-2-(2- methoxyphenyl)-3- methyl- pyrazolo[5,1- b]pyrimidin-7-ol ##STR00194## 5-[2-(3,5-dimethyl- 1H-pyrazol-4- yl)ethyl]-3-methyl- 2-(2- thienyl)pyrazolo[5,1- b]pyrimidin-7-ol ##STR00195## IUPAC Name: 3-(4-chlorophenyl)- 5-[2-(3,5-dimethyl- 1H-pyrazol-4-yl)- ethyl]-2-methyl-1H- pyrazolo[1,5-a]- pyrimidin-7-one ##STR00196## IUPAC Name: 5-[2-(3,5-dimethyl- 1H-pyrazol-4-yl)- ethyl]- 2-methyl-3-phenyl- 1H-pyrazolo[1,5-a]- pyrimidin-7-one ##STR00197## 5-[2-(3,5-dimethyl- 1H-pyrazol-4- yl)ethyl]-2-(4- fluorophenyl)- pyrazolo[5,1- b]pyrimidin-7-o ##STR00198## IUPAC Name: 3-(4-chlorophenyl)- 5-[2-(3,5-dimethyl- 1H-pyrazol-4-yl)- ethyl]-1H-pyrazolo- [1,5-a]pyrimidin- 7-one ##STR00199##

[0076] Compounds of Table 1 can be found on http:\\zinc.docking.org.

[0077] FIG. 17 gives an overview of the inhibitory effects of these small inhibitory compounds on MKK4 protein in relation to the inhibition by Genistein.

[0078] In vitro testing according to Example 4 and in vivo testing according to Example 6 could show that these small inhibitory compounds are suitable for use as a medicament for the treatment of liver failure and/or for the protection of hepatocytes against apoptosis and/or for the regeneration of hepatocytes.

Sequence CWU 1

1

1204121RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 1uuugugaaca cuauacaccc u 21221RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 2uuuauuacaa cugaccugca g 21321RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 3uuaaacagca ccauucuccc u 21421RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 4uugugaacac uauacacccu u 21521RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 5uagagucuga uguagcagcg a 21621RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 6uucacuguca uacaaagccu a 21721RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 7uaaucuauga uuaauacacu a 21821RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 8auacauugua auaaacuccu u 21921RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 9uacauuguaa uaaacuccuu g 211021RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 10uucuggaaua acaucaucua a 211121RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 11acagucaaca acuugaucgu a 211221RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 12uucaacuuca gugcuuugcg u 211321RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 13uaucaaucga cauacauggg a 211421RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 14uaauuuaaca ugauauuuca a 211521RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 15uuugacagua uuuaugacug u 211621RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 16aauauuucca cuucugucca g 211721RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 17uacauaaaca cuucgauucc a 211821RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 18uuauaguuua uaauaaucua u 211921RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 19uaguuuauaa uaaucuauga u 212021RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 20uuccaguagc ugcaucucca g 212121RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 21ugugacuuua aacagcacca u 212221RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 22uuggauaagg aaaucggccu g 212321RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 23uagaaaucuu uaucuaauca a 212421RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 24uagagcaaug ucuccuuuca g 212521RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 25uauccuuguc gugaugcgcu u 212621RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 26uaaucuauug cacuugguga a 212721RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 27uuuaucaccu accacaucgg c 212821RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 28ucaacuguaa cuguaaagca a 212921RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 29uaaacuuugc cuucuguacu g 213021RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 30uugggauuca gaguaaaccu u 213121RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 31uacagaucca acagucaccc u 213221RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 32uacacuauau acauauuugu a 213321RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 33uuuauaguuu auaauaaucu a 213421RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 34uaaagcaaca gaauaucaca u 213521RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 35ucuuguaaca gugcugaggg u 213621RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 36uaaacagcac cauucucccu u 213721RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 37augaguucca uacagaucca a 213821RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 38uuauugcaca uggugucugg g 213921RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 39uugaucaaau acacuauucc a 214021RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 40uaauauuucc acuucugucc a 214121RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 41uucuagcagg ugaugaacgu a 214221RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 42uuccucagaa uuacucagcu g 214321RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 43uuaguugauc aaauacacua u 214421RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 44agauuuauua caacugaccu g 214521RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 45uaacaucauc uaauacacua u 214621RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 46uaagauguga ucuaaucaca g 214721RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 47uuguugggag ugaagagccg a 214821RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 48uauauaucuu aaauagagga g 214921RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 49uugcuguaga uuugaaaggu g 215021RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 50uuucuucugg aauaacauca u 215121RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 51ucauccacac aauagaacgg u 215221RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 52uuguaauaaa cuccuugccc u 215321RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA 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gucacauagc g

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2111121RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 111uagauuugaa agguggauuu g 2111221RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 112uugggucuau ucuuucaggu g 2111321RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 113uuaucaccua ccacaucggc u 2111421RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 114agaacuauua cauaaacacu u 2111521RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 115ucuucuuuca guccuggugg u 2111621RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 116ugacagaacc auaagcuccu c 2111721RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 117uuuauaauaa ucuaugauua a 2111821RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 118uacgagaggu ucuagcaggu g 2111921RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 119uuuaugacug ucacucugag a 2112021RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 120auucuuuacg ucuugcuucc u 2112121RNAArtificial Sequencesource1..21/mol_type="RNA" 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/organism="Artificial

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2113721RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 137uugaucguac ugacuuccac a 2113821RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 138auaucuuaaa uagaggagga a 2113921RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 139uucuucugga auaacaucau c 2114021RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 140auaaccagag cucacaaugu a 2114121RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 141uauuccacuu uggauaagga a 2114221RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 142uuaaauagag gaggaauuca a 2114321RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 143auuuaugacu gucacucuga g 2114421RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 144ucuugcuucc ucucagcccu u 2114521RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 145uugacaaagu ugaugaaacu c 2114621RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 146uagcaugcga ccucaacggc a 2114721RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 147uauguuacug agcuccauuu u 2114821RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 148auccuugucg ugaugcgcuu g 2114921RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 149uuauuguuug acaguauuua u 2115021RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 150uaucccugca cauuagcuuu u 2115121RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 151uauuguuuga caguauuuau g 2115221RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 152ucagcugcgg aggaucuccu u 2115321RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 153uacuccgcau uacuacaucc a 2115421RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 154cugaccagca cuaacacugu g 2115521RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 155uaagugaaga agcacaagau a 2115621RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 156uucagaagcu cuuuauacuu u 2115721RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 157ugaauuuaag augugaucua a 2115821RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 158ucacauagcg acaauagacc a 2115921RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 159uccuuugucu cccagcucca g 2116021RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 160aauuucucca aggucuuuca a 2116121RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 161auagagucca caagcugucc a 2116221RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 162uccuagauuu auuacaacug a 2116321RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 163ucgacauaca ugggagagcu g 2116421RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 164ucaaucaggu auuacaagga u 2116521RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 165cuaaucacag ucaacaacuu g 2116621RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 166aucaaauaca cuauuccacu u 2116721RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 167auucggaaac ugaagaccug g 2116821RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 168auguucaccu cuuugaacgc a 2116921RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 169uacuagcuac uucucccugu u 2117021RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 170aacaccaauc uuauugcaca u 2117121RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 171ucggauccuc aucuggucca a 2117221RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 172auacacuaua uacauauuug u 2117321RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 173aaacuccaga caucagagcg g 2117421RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 174aaacaacuga gauuuggucu u 2117521RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 175uugcguuuac ccugcaugcu g 2117621RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 176uaaucacagu caacaacuug a 2117721RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 177acuauuacau aaacacuucg a 2117821RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 178ugucauacaa agccuaaggu u 2117921RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 179uauguucaga cauaguacau u 2118021RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 180acaacuugau cguacugacu u 2118121RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 181uuaggaucag caccuucuuu g 2118221RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 182ugaucguacu gacuuccaca u 2118321RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 183auuguuggga gugaagagcc g 2118421RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 184uauagcugcu acaaguuguu c 2118521RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 185uuugaacgca acaugguuuu u 2118621RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 186uccaguagaa uuccaaugcc a 2118721RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 187aagcugucca cugaugccga a 2118821RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 188uagugcuuuc acaguugcua a 2118921RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA

encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 189uuaucaaacg agguagacau g 2119021RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 190ugguaaggaa caucccugcu a 2119121RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 191uuugauaucu cugugaauaa u 2119221RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 192uagcugcuac aaguuguucc a 2119321RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 193aaacuuugcc uucuguacug u 2119421RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial 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2120521RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 205aauuccuccu uugucuccca g 2120621RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 206aucaccuacc acaucggcug g 2120721RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 207ucuguccaga agaauauugg a 2120821RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 208aaaguugaug aaacucgggg a 2120921RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 209auacacuauu ccacuuugga u 2121021RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 210uaugacuguc acucugagag g 2121121RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 211aauucugcaa uuuacaggga u 2121221RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 212auuacaagga ugcacguucu a 2121321RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 213uuaugugguc auccacacaa u 2121421RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 214ucacucugag aggagacaca g 2121521RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 215ucuuugaacg caacaugguu u 2121621RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 216uccaauuucu ccaaggucuu u 2121721RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 217uaacuguaaa gcaacagaau a 2121821RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 218aaaguuuagg auaccguggg g 2121921RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 219uucagaacag ugggaagucu a 2122021RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 220ugcugcuuca cugucauaca a 2122121RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 221uccucugcag ugaaauccca g 2122221RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 222uuaugacugu cacucugaga g 2122321RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 223aauaucacau caguaaucua u 2122421RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 224aucaccugca ucucaggcca u 2122521RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 225ugugcuugaa ccacucacag u 2122621RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 226aauaacauca ucuaauacac u 2122721RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 227auugcuacua gcuacuucuc c 2122821RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 228uucggaaacu gaagaccugg a 2122921RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 229auuuauuaca acugaccugc a 2123021RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 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2123621RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 236aauucaaaca agaauacagg a 2123721RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 237uacaguucuu acacuauuuu c 2123821RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 238agcugcuaca aguuguucca g 2123921RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 239ucagaguaaa ccuugcugua g 2124021RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 240uuucaagucc ucugcaguga a 2124121RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 241uagcgacaau agaccacagg g 2124221RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 242aacuccagac aucagagcgg a 2124321RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 243auagcgacaa uagaccacag g 2124421RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 244uaucaaacga gguagacaug a 2124521RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 245ugaauucugc aauuuacagg g 2124621RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 246uaggugacag gaguauacag a 2124721RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 247ucugaccagc acuaacacug u 2124821RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 248aguuauguua cugagcucca u 2124921RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 249uaaggcaaua ucccugcaca u 2125021RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 250uuacaaggau gcacguucua g 2125121RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 251uguucucagu cucucuaugu g 2125221RNAArtificial

Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 252aacacauucu guccugucuc u 2125321RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 253uucauccuuc guaaggcaca a 2125421RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 254aaguugacag cagagaaaca g 2125521RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 255ucuguaaacu uugccuucug u 2125621RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 256uuaagaugug aucuaaucac a 2125721RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 257augaacguaa aggcugccgu u 2125821RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 258uuagcuccug gacagucaga a 2125921RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 259auucagagua aaccuugcug u 2126021RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 260ugaaauccca guguuguuca g 2126121RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 261uauuacaacu gaccugcagg c 2126221RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 262uugcuacuag cuacuucucc c 2126321RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 263uuugcguuua cccugcaugc u 2126421RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 264auguauauau cuuaaauaga g 2126521RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 265aaauacacua uuccacuuug g 2126621RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 266aaacacuucg auuccaugua u 2126721RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 267acauagagca augucuccuu u 2126821RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 268ugggcaauca cuacuccgca u 2126921RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 269aucuaauaca cuauauacau a 2127021RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 270uucuguccug ucucuauauu u 2127121RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 271ugaagaagca caagauacuu a 2127221RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 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2127821RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 278ucuaauacac uauauacaua u 2127921RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 279ucgauuccau guauauaucu u 2128021RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 280ugggagugaa gagccgagcg g 2128121RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 281uuauuacaac ugaccugcag g 2128221RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 282uuccaggauu uggaagucug a 2128321RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 283auccucaucu gguccaaugu g 2128421RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 284uuccauacag auccaacagu c 2128521RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 285uuucaguccu ggugguuugu g 2128621RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 286auaguuuaua auaaucuaug a 2128721RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 287uuacauaaac acuucgauuc c 2128821RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 288acaagcuguc cacugaugcc g 2128921RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 289aaacauagca ugcgaccuca a 2129021RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 290uagacaugag uuccauacag a 2129121RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 291aacaucaucu aauacacuau a 2129221RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 292uauuucaaac aggaaauuug g 2129321RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 293uggacaguca gaauugcuuu u 2129421RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 294aacucauaca augugauccc c 2129521RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 295uaugugguca uccacacaau a 2129621RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 296aauaucccug cacauuagcu u 2129721RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 297ucacaucagu aaucuauugc a 2129821RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial 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2130921RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 309uugaaccacu cacagugcug c 2131021RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 310uccuucguaa ggcacaaguu g 2131121RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 311uacacuauuc cacuuuggau a 2131221RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 312acaaauaagg caauaucccu g 2131321RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 313auucauucua auuuaacaug a 2131421RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 314aaucaaggca cauugcuacu a

2131521RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 315uccaaggucu uucaaguccu c 2131621RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 316gucaacaacu ugaucguacu g 2131721RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 317aaauucauuc uaauuuaaca u 2131821RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 318uauuugccca cuugguuugu g 2131921RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 319uccaacaguc acccucucug a 2132021RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 320ugccucuuua ucaccuacca c 2132121RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 321uucgauucca uguauauauc u 2132221RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 322cauaguacau ucaucacugu g 2132321RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 323ucucccuuua uuguuugaca g 2132421RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 324caaacaucaa cuguaacugu a 2132521RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 325aaguuuagga uaccgugggg g 2132621RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 326aacuuugccu ucuguacugu u 2132721RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 327uuucaugaau auguucauca c 2132821RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 328aagguuugau aucucuguga a 2132921RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 329uuauuugccc acuugguuug u 2133021RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 330uaauaaucua ugauuaauac a 2133121RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 331uccaguagcu gcaucuccag g 2133221RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 332uugcccuuaa guuuauaguu u 2133321RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 333auuccagugu gcuugaacca c 2133421RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 334uacagacaug auggaaacga a 2133521RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial 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340aucaaucaag gcacauugcu a 2134121RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 341auagaggagg aauucaaaca a 2134221RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 342uuauguuacu gagcuccauu u 2134321RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 343cauuacuaca uccaaaucca u 2134421RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 344ucaccucuuu gaacgcaaca u 2134521RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 345aacaugauau uucaaacagg a 2134621RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 346aucuuuaucu aaucaaucaa g 2134721RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 347auccuagauu uauuacaacu g 2134821RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 348uaaauuccuc cuuugucucc c 2134921RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 349acuguaacug uaaagcaaca g 2135021RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 350uguugacaga accauaagcu c 2135121RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 351ucaguaaucu auugcacuug g 2135221RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 352uccuguagga uugggauuca g 2135321RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 353uagaucaaag agauaaucac u 2135421RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 354ugggagagcu gggaguagcu g 2135521RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 355uggucgaagg cagacauaga g 2135621RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 356ugcacguucu aggugacagg a 2135721RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 357agacauagag caaugucucc u 2135821RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 358aaucuuauug cacauggugu c 2135921RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 359aucaacugua acuguaaagc a 2136021RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 360uagcugcauc uccagguuuu g 2136121RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 361aacagcacca uucucccuuu a 2136221RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 362uaggauuggg auucagagua a 2136321RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 363aaucuaugau uaauacacua a 2136421RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 364uggaaacgaa caccaaucuu a 2136521RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 365ucacagugcu gcuucacugu c 2136621RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 366aguaaucuau ugcacuuggu g 2136721RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 367uaucuaauca aucaaggcac a 2136821RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 368uuucagaaca gugggaaguc u 2136921RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 369ucagaagcuc uuuauacuuu g 2137021RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 370uaggaucagc accuucuuug a 2137121RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 371uauuggaagg uuugauaucu c 2137221RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 372uauugcacau ggugucuggg c 2137321RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 373aucuaaucaa ucaaggcaca u 2137421RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 374ugggauucag aguaaaccuu g 2137521RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 375aucagcaccu ucuuugacaa g 2137621RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 376aagccuaagg uucagugcca g 2137721RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial

Sequence"ncRNA1..21/ncRNA_class="siRNA" 377uccugaugac ucaaugcugu g 2137821RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 378uaauggguaa gugaagaagc a 2137921RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 379uucacaguug cuaaagugau u 2138021RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 380uaucaggcuu gggaccaagg g 2138121RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 381aaacaucaac uguaacugua a 2138221RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 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2138821RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 388ucauucuaau uuaacaugau a 2138921RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 389ucagguauua caaggaugca c 2139021RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 390uagcagguga ugaacguaaa g 2139121RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 391aaacacuagc gaauaugaga g 2139221RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 392aaucaaucaa ggcacauugc u 2139321RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 393ucuuaugugg ucauccacac a 2139421RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 394ugaagaaagu aaauuccucc u 2139521RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 395uucuauguuc agacauagua c 2139621RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 396ugaggucucu cugaccagca c 2139721RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 397ucuauugcac uuggugaaga a 2139821RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 398auucuuagga ucagcaccuu c 2139921RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 399uguaacagug cugaggguuu u 2140021RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 400aucaaucgac auacauggga g 2140121RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 401cuauuacaua aacacuucga u 2140221RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 402ucacugucau acaaagccua a 2140321RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 403uuauaauaau cuaugauuaa u 2140421RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 404ugugaacacu auacacccuu u 2140521RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 405uuuccucaga auuacucagc u 2140621RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 406ugauguagca gcgauaucaa u 2140721RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 407augcgcuugg gucuauucuu u 2140821RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial 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2141921RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 419uaaacacuag cgaauaugag a 2142021RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 420uagcgaauau gagagauuug g 2142121RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 421uggauuaagc gcaagucaca u 2142221RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 422ucacccucuc ugaagagugc a 2142321RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 423uccacauuuc augaauaugu u 2142421RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 424aauacacuau uccacuuugg a 2142521RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 425acaccauucc aguagcugca u 2142621RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 426uucuuaugug gucauccaca c 2142721RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 427ugaucaauca gguauuacaa g 2142821RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 428ucguccaauu ucuccaaggu c 2142921RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 429ucccuuuauu guuugacagu a 2143021RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 430ucagaauuac ucagcugcgg a 2143121RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 431ugaggcaagu agaucaaaga g 2143221RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 432uuuaaacagc accauucucc c 2143321RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 433auaucccugc acauuagcuu u 2143421RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 434ucaaucgaca uacaugggag a 2143521RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 435uggugaagaa aguaaauucc u 2143621RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 436augauggaaa cgaacaccaa u 2143721RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 437auagcaugcg accucaacgg c 2143821RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 438augggcaauc acuacuccgc a 2143921RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 439uucuguccag aagaauauug g 2144021RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA

encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 440aucacaguca acaacuugau c 2144121RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 441uacuagaaau cuuuaucuaa u 2144221RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 442aaucccagug uuguucaggg g 2144321RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 443aagaauauug gaagguuuga u 2144421RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 444ucaaacaaga auacaggaua a 2144521RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial 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2145621RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 456aagaugugau cuaaucacag u 2145721RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 457acuuuaaaca gcaccauucu c 2145821RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 458auuacuacau ccaaauccau a 2145921RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 459ucuucuggaa uaacaucauc u 2146021RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 460acuccgcauu acuacaucca a 2146121RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 461aacuugaucg uacugacuuc c 2146221RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 462auaaucuaug auuaauacac u 2146321RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 463acauaaacac uucgauucca u 2146421RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 464uccagaagaa uauuggaagg u 2146521RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 465ugagucuaga aaugaauuua a 2146621RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 466uguuaguuga ucaaauacac u 2146721RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 467uuuaacauga uauuucaaac a 2146821RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 468aaugucuccu uucagaacag u 2146921RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 469uggaauaaca ucaucuaaua c 2147021RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 470aucagguauu acaaggaugc a 2147121RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 471ugcacauggu gucugggcga g 2147221RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 472ucuauguuca gacauaguac a 2147321RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 473uuuacaggga ugugacuuua a 2147421RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 474gauucggaaa cugaagaccu g 2147521RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 475ugaacacuau acacccuuuu g 2147621RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial 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2148721RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 487uacugacuuc cacauuucau g 2148821RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 488auuucuucug gaauaacauc a 2148921RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 489agagcggaca ucauauccuu g 2149021RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 490ugcagugaaa ucccaguguu g 2149121RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 491uuacccugca ugcugcugac g 2149221RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 492uaagugguuu agugcuuuca c 2149321RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 493ucuagaaaug aauuuaagau g 2149421RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 494auccaaaucc auaagaaguu g 2149521RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 495acagcagaga aacagauucc u 2149621RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 496uccagugugc uugaaccacu c 2149721RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 497uuugcccacu ugguuugugg a 2149821RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 498ucugcaguga aaucccagug u 2149921RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 499acaaacauag caugcgaccu c 2150021RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 500uguucagaca uaguacauuc a 2150121RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 501ucaucuaaua cacuauauac a 2150221RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 502agcucuucuc acucaagccc g 2150321RNAArtificial

Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 503accaaucuua uugcacaugg u 2150421RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 504aaucacuacu ccgcauuacu a 2150521RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 505ucguaaggca caaguugaca a 2150621RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 506uggauaagga aaucggccug u 2150721RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 507ucugcaauuu acagggaugu g 2150821RNAArtificial Sequencesource1..21/mol_type="RNA" 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2152921RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 529uucaaguccu cugcagugaa a 2153021RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 530ugcaugcugc ugacggccgg g 2153121RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 531ucagauuagc uccuggacag u 2153221RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 532ucaaacgagg uagacaugag u 2153321RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 533ugcuguagau uugaaaggug g 2153421RNAArtificial 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2156021RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 560uaaauagagg aggaauucaa a 2156121RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 561aagcacaaga uacuuaaaug g 2156221RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 562cugacuucca cauuucauga a 2156321RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 563uacuucuccc uguuagugag u 2156421RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 564auuggaaggu uugauaucuc u 2156521RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 565uggugaugga cuacgagagg u

2156621RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 566auacagaucc aacagucacc c 2156721RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 567uugcccacuu gguuugugga c 2156821RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 568aacacuagcg aauaugagag a 2156921RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 569agacacagca auacgugcca c 2157021RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 570aucaaggcac auugcuacua g 2157121RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 571ucaagcccga guuucuaugu u 2157221RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 572uugauaucuc ugugaauaau u 2157321RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 573ugucuccuuu cagaacagug g 2157421RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 574cacagucaac aacuugaucg u 2157521RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 575uucaaacaag aauacaggau a 2157621RNAArtificial Sequencesource1..21/mol_type="RNA" 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2159721RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 597auccaacagu cacccucucu g 2159821RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 598aucaggcuug ggaccaaggg g 2159921RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 599uguucaccuc uuugaacgca a 2160021RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 600aagcgcaagu cacauagcga c 2160121RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 601uugccuucuu auguggucau c 2160221RNAArtificial 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2162821RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial

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Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 675uucguaaggc acaaguugac a 2167621RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 676caacuugauc guacugacuu c 2167721RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 677acaucaucua auacacuaua u 2167821RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 678uaauaaacuc cuugcccuua a 2167921RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 679aacuguaaag caacagaaua u 2168021RNAArtificial Sequencesource1..21/mol_type="RNA" 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2170721RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 707ucuuuacguc uugcuuccuc u 2170821RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 708uauaauaauc uaugauuaau a 2170921RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 709aaaucuuuau cuaaucaauc a 2171021RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 710uuccauguau auaucuuaaa u 2171121RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 711uccauacaga uccaacaguc a 2171221RNAArtificial 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Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 816gacuacgaga gguucuagca g

2181721RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 817aacuccugua ggauugggau u 2181821RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 818agaagcaaac aacugagauu u 2181921RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 819agacaugagu uccauacaga u 2182021RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 820augaauaugu ucaucacaaa a 2182121RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 821cuugcuguag auuugaaagg u 2182221RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 822gaacacauuc uguccugucu c 2182321RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 823aggaugaggu cucucugacc a 2182421RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 824uacaaguugu uccagauaaa a 2182521RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 825aaauauauag cugcuacaag u 2182621RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 826acaguauuua ugacugucac u 2182721RNAArtificial Sequencesource1..21/mol_type="RNA" 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Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 853ugacuuccac auuucaugaa u 2185421RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 854aauagaacgg ucagauuagc u 2185521RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 855cuguagauuu gaaaggugga u 2185621RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 856ugcuacaagu uguuccagau a 2185721RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 857caagaagcaa acaacugaga u 2185821RNAArtificial Sequencesource1..21/mol_type="RNA" 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2187921RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial

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2189021RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 890aaggaacauc ccugcuaacu g 2189121RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 891gaagguuuga uaucucugug a 2189221RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 892gauucagagu aaaccuugcu g 2189321RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 893gaucguacug acuuccacau u 2189421RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 894cuguccagaa gaauauugga a 2189521RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 895ucauccacug uugaccgaau u 2189621RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 896aauaaucuau gauuaauaca c 2189721RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 897cauugcuacu agcuacuucu c 2189821RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 898acaguuugug aacacuauac a 2189921RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 899acuugguuug uggaccauuu u 2190021RNAArtificial Sequencesource1..21/mol_type="RNA" 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Sequence"ncRNA1..21/ncRNA_class="siRNA" 910cagacuccug agucuuccca u 2191121RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 911ucccuguuag ugaguuauga u 2191221RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 912acaucaguaa ucuauugcac u 2191321RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 913aaaguaaauu ccuccuuugu c 2191421RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 914aagauaaauu cauucuaauu u 2191521RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 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Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 926caaagcucca agaagcaguu a 2192721RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 927ugacagcaga gaaacagauu c 2192821RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 928ccucuuugaa cgcaacaugg u 2192921RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 929ugagaggaga cacagcaaua c 2193021RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 930guaaucuauu gcacuuggug a 2193121RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 931aagaagcaca agauacuuaa a 2193221RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 932gauaucucug ugaauaauuu u 2193321RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 933aucuauugca cuuggugaag a 2193421RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 934auauuggaag guuugauauc u 2193521RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 935gauacauugu aauaaacucc u 2193621RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" 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Sequence"ncRNA1..21/ncRNA_class="siRNA" 941uagcuacuuc ucccuguuag u 2194221RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA

encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 942cucuucucac ucaagcccga g 2194321RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 943auguaugggc aaucacuacu c 2194421RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 944cauuguaaua aacuccuugc c 2194521RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 945cuguaaacuu ugccuucugu a 2194621RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 946cagaaccaua agcuccucgu c 2194721RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 947aaacuccuug cccuuaaguu u 2194821RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 948aacugaagac cuggaccagu g 2194921RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 949aucgacauac augggagagc u 2195021RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 950uuuccacuuc uguccagaag a 2195121RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 951cugaagaccu ggaccaguga u 2195221RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 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2195821RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 958agauucggaa acugaagacc u 2195921RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 959acauugcuac uagcuacuuc u 2196021RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 960caguagcugc aucuccaggu u 2196121RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 961auaucacauc aguaaucuau u 2196221RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 962aagucacaua gcgacaauag a 2196321RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 963guaugggcaa ucacuacucc g 2196421RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 964uggauucauc cuucguaagg c 2196521RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 965aaguaaauuc cuccuuuguc u 2196621RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 966auaaagauac auuguaauaa a 2196721RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 967caugaguucc auacagaucc a 2196821RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 968acaucaacug uaacuguaaa g 2196921RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 969cauagcaugc gaccucaacg g 2197021RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 970aguccacaag cuguccacug a 2197121RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 971acaggaguau acagacauga u 2197221RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 972agaacacauu cuguccuguc u 2197321RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" 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Sequence"ncRNA1..21/ncRNA_class="siRNA" 978auauuggauu aagcgcaagu c 2197921RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 979ucauacaaag ccuaagguuc a 2198021RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 980uguagauuug aaagguggau u 2198121RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 981uucagugcuu ugcguuuacc c 2198221RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 982auagcugcua caaguuguuc c 2198321RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 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2198921RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 989guccacaagc uguccacuga u 2199021RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 990uagggaaaug aggcaaguag a 2199121RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 991acggucagau uagcuccugg a 2199221RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 992agaaaucuuu aucuaaucaa u 2199321RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 993cuuaauauuu ccacuucugu c 2199421RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 994cacaaguuga caaaguugau g 2199521RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 995cugccuacua gaaaucuuua u 2199621RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 996acaugaugga aacgaacacc a 2199721RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 997acuucugucc agaagaauau u 2199821RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 998uuccacuuug gauaaggaaa u 2199921RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 999agauaaauuc auucuaauuu a 21100021RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 1000ggucuuucaa guccucugca g 21100121RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 1001aagagauucg gaaacugaag a 21100221RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 1002guacaguucu uacacuauuu u 21100321RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 1003cauacaaagc cuaagguuca g 21100421RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 1004aauuuacagg gaugugacuu u 21100521RNAArtificial

Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 1005aguuucuaug uucagacaua g 21100621RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 1006aggaguauac agacaugaug g 21100721RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 1007aaugaauuua agaugugauc u 21100821RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 1008ggcaauagag uccacaagcu g 21100921RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 1009aacaucccug cuaacuguaa a 21101021RNAArtificial Sequencesource1..21/mol_type="RNA" 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encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 1015uacagacaaa uaaggcaaua u 21101621RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 1016gcacauugcu acuagcuacu u 21101721RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 1017agacaugaug gaaacgaaca c 21101821RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 1018guagcagcga uaucaaucga c 21101921RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 1019auguuucaga agcucuuuau a 21102021RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" 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Sequence"ncRNA1..21/ncRNA_class="siRNA" 1025auauuccaaa gcuccaagaa g 21102621RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 1026caggauuugg aagucugaca a 21102721RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 1027agucacauag cgacaauaga c 21102821RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 1028agaaacagau uccucuugag u 21102921RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 1029uaaauucauu cuaauuuaac a 21103021RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 1030aagaagcagu uauguuacug a 21103121RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 1031ugaagaccug gaccagugau g 21103221RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 1032cgagguagac augaguucca u 21103321RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 1033aaccacucac agugcugcuu c 21103421RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 1034gugacaggag uauacagaca u 21103521RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 1035aucacauccu agauuuauua c 21103621RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 1036caauuuacag ggaugugacu u 21103721RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 1037aacuccuugc ccuuaaguuu a 21103821RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 1038cucugaccag cacuaacacu g 21103921RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 1039aucauauccu ugucgugaug c 21104021RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 1040uccacugaug ccgaagucac a 21104121RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 1041gucuauucuu ucaggugcca u 21104221RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 1042uuucuccaag gucuuucaag u 21104321RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 1043agcagagaaa cagauuccuc u 21104421RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 1044auacauggga gagcugggag u 21104521RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 1045acaauagaac ggucagauua g 21104621RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 1046gucgugaugc gcuugggucu a 21104721RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 1047caaucuuauu gcacauggug u 21104821RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 1048agaaauggug auggacuacg a 21104921RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 1049aacuguaacu guaaagcaac a 21105021RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 1050agugcuuuca caguugcuaa a 21105121RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 1051guaaagauaa auucauucua a 21105221RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 1052caaucgacau acaugggaga g 21105321RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 1053ggaugagguc ucucugacca g 21105421RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 1054auuccaaagc uccaagaagc a 21105521RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 1055caggaguaua cagacaugau g 21105621RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 1056agcucacaau guacaguucu u 21105721RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 1057acagaauauc acaucaguaa u 21105821RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 1058gagaaacaga uuccucuuga g 21105921RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 1059acaugguguc ugggcgagca a 21106021RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 1060cacuacuccg cauuacuaca u 21106121RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 1061caggugauga acguaaaggc u 21106221RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 1062uguaaacuuu gccuucugua c 21106321RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 1063gauaucaauc gacauacaug g 21106421RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 1064uggucaucca cacaauagaa c 21106521RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 1065ugauggacua cgagagguuc u 21106621RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 1066aagagccgag cggcgccgcg g 21106721RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 1067acuuugccuu cuguacuguu u

21106821RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 1068cagcacaccg aauucugaga a 21106921RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 1069aggaauucaa acaagaauac a 21107021RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 1070gacaaauaag gcaauauccc u 21107121RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 1071ucuccaaggu cuuucaaguc c 21107221RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 1072gaguccacaa gcuguccacu g 21107321RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 1073acugaagacc uggaccagug a 21107421RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 1074aucuaaucac agucaacaac u 21107521RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 1075acuauauaca uauuuguaaa a 21107621RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 1076uccucagaau uacucagcug c 21107721RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 1077gaagauaggg aaaugaggca a 21107821RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 1078cucugcagug aaaucccagu g 21107921RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 1079gaacuauuac auaaacacuu c 21108021RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 1080caaacaacug agauuugguc u 21108121RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 1081gauuagcucc uggacaguca g 21108221RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 1082uauauuccag ugugcuugaa c 21108321RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 1083cucuuguaac agugcugagg g 21108421RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 1084auagggaaau gaggcaagua g 21108521RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 1085uguccagaag aauauuggaa g 21108621RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 1086gucuugcuuc cucucagccc u 21108721RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 1087cuugguuugu ggaccauuuu g 21108821RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 1088augggaaguu gacagcagag a 21108921RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 1089uccagacauc agagcggaca u 21109021RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 1090caauagaguc cacaagcugu c 21109121RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 1091uaaggaacau cccugcuaac u 21109221RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 1092cuuuacgucu ugcuuccucu c 21109321RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 1093cuccugaguc uucccauuga a 21109421RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 1094agcaaacaac ugagauuugg u 21109521RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 1095cuacuucucc cuguuaguga g 21109621RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 1096agucuaaagu uuaggauacc g 21109721RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 1097aauauuggaa gguuugauau c 21109821RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 1098ugaauauguu caucacaaaa g 21109921RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 1099gaaaugaggc aaguagauca a 21110021RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 1100auguucagac auaguacauu c 21110121RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 1101caucaucaca uccuagauuu a 21110221RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 1102caucuguaaa cuuugccuuc u 21110321RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 1103caaacauagc augcgaccuc a 21110421RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 1104cucacagugc ugcuucacug u 21110521RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 1105caaggucuuu caaguccucu g 21110621RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 1106cuaauuuaac augauauuuc a 21110721RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 1107acauuguaau aaacuccuug c 21110821RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 1108gaugccgaag ucacagagcu u 21110921RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 1109caaugucucc uuucagaaca g 21111021RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 1110agaaccauaa gcuccucguc c 21111121RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 1111guucuagcag gugaugaacg u 21111221RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 1112guaacuguaa agcaacagaa u 21111321RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 1113guaagugaag aagcacaaga u 21111421RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 1114aaagcuccaa gaagcaguua u 21111521RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 1115caccauucuc ccuuuauugu u 21111621RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 1116acuccugagu cuucccauug a 21111721RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 1117caaacuccag acaucagagc g 21111821RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 1118auucucccuu uauuguuuga c 21111921RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 1119caccucuuug aacgcaacau g 21112021RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 1120ucaaggcaca uugcuacuag c 21112121RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 1121cagacauaga gcaaugucuc c 21112221RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 1122caagaagcag uuauguuacu g 21112321RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 1123acauccuaga uuuauuacaa c 21112421RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 1124gaaacgaaca ccaaucuuau u 21112521RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 1125ugguaaagau aaauucauuc u 21112621RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 1126ccaacaguca cccucucuga a 21112721RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 1127cagcagagaa acagauuccu c 21112821RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 1128caaacgaggu agacaugagu u 21112921RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 1129cuuuauuguu ugacaguauu u 21113021RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial

Sequence"ncRNA1..21/ncRNA_class="siRNA" 1130auaauaaucu augauuaaua c 21113121RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 1131caaauccaua agaaguuguu u 21113221RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 1132ucacuacucc gcauuacuac a 21113321RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 1133acuacaucca aauccauaag a 21113421RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 1134ucagcaccuu cuuugacaag u 21113521RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 1135aguuugugaa cacuauacac c 21113621RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 1136aacaauguau gggcaaucac u 21113721RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 1137uaggacuggu aaaggagaaa a 21113821RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 1138gcuugaacca cucacagugc u 21113921RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 1139agaugggaag uugacagcag a 21114021RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 1140gcagacuccu gagucuuccc a 21114121RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 1141augcgaccuc aacggcacgu u 21114221RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 1142agaauuacuc agcugcggag g 21114321RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 1143ucucucugac cagcacuaac a 21114421RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 1144cugucauaca aagccuaagg u 21114521RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 1145ucugaagagu gcaccauaaa a 21114621RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 1146caaauacacu auuccacuuu g 21114721RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 1147auacaaagcc uaagguucag u 21114821RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 1148aacgagguag acaugaguuc c 21114921RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 1149aaagauaaau ucauucuaau u 21115021RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 1150ugaagagccg agcggcgccg c 21115121RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 1151acaaguugac aaaguugaug a 21115221RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 1152ccuucuuaug uggucaucca c 21115321RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 1153acuucucccu guuagugagu u 21115421RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial Sequence"ncRNA1..21/ncRNA_class="siRNA" 1154agcccgaguu ucuauguuca g 21115521RNAArtificial Sequencesource1..21/mol_type="RNA" /note="siRNA specific for mRNA encoding MKK4" /organism="Artificial 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caaguuguug acugugauua 1560gaucacaucu uaaauucauu ucuagacuca aaaccuggag augcagcuac uggaauggug 1620uuuugucaga cuuccaaauc cuggaaggac acagugauga auguacuaug ucugaacaua 1680gaaacucggg cuugagugag aagagcuugc acagccaacg agacacauug ccuucuggag 1740cugggagaca aaggaggaau uuacuuucuu caccaagugc aauagauuac ugaugugaua 1800uucuguugcu uuacaguuac aguugauguu uggggaucga ugugcucagc caaauuuccu 1860guuugaaaua ucauguuaaa uuagaaugaa uuuaucuuua ccaaaaacca uguugcguuc 1920aaagagguga acauuaaaau auagagacag gacagaaugu guucuuuucu ccuuuaccag 1980uccuauuuuu caaugggaag acucaggagu cugccacuug ucaaagaagg ugcugauccu 2040aagaauuuuu cauucucaga auucggugug cugccaacuu gauguuccac cugccacaaa 2100ccaccaggac ugaaagaaga aaacaguaca gaaggcaaag uuuacagaug uuuuuaauuc 2160uaguauuuua ucuggaacaa cuuguagcag cuauauauuu ccccuugguc ccaagccuga 2220uacuuuagcc aucauaacuc acuaacaggg agaaguagcu aguagcaaug ugccuugauu 2280gauuagauaa agauuucuag uaggcagcaa aagaccaaau cucaguuguu ugcuucuugc 2340caucacuggu ccaggucuuc aguuuccgaa ucucuuuccc uuccccugug 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3240auagggucac uuugccauua ugcaaaugga gauaaaagca auucugacug uccaggagcu 3300aaucugaccg uucuauugug uggaugacca cauaagaagg caauuuuagu guauuaauca 3360uagauuauua uaaacuauaa acuuaagggc aaggaguuua uuacaaugua ucuuuauuaa 3420aacaaaaggg uguauagugu ucacaaacug ugaaaauagu guaagaacug uacauuguga 3480gcucugguua uuuuucucuu guaccauaga aaaauguaua aaaauuauca aaaagcuaau 3540gugcagggau auugccuuau uugucuguaa aaaauggagc ucaguaacau aacugcuucu 3600uggagcuuug gaauauuuua uccuguauuc uuguuugaau uccuccucua uuuaagauau 3660auacauggaa ucgaaguguu uauguaauag uucuauccuu uugccugcag gucaguugua 3720auaaaucuag gaugugauga ugaaaaaaaa aa 3752

Claims

1. A method of treatment of liver failure and/or for the treatment of impaired liver function and/or for the protection of hepatocytes against apoptosis and/or for the regeneration of hepatocytes, the method comprising a step of administering to a patient in need of treatment a compound, which is an inhibitor of the activity of MKK4, wherein said MKK4 is encoded by mRNA with SEQ ID NO: 1204, wherein the compound is not SP600125, myricitine, PD98059, genistein, or ZM 336372.

2. The method according to claim 1, wherein the compound is at least one of the following: ##STR00200## ##STR00201## ##STR00202## ##STR00203## ##STR00204## ##STR00205## ##STR00206## ##STR00207## ##STR00208## ##STR00209## ##STR00210## ##STR00211## ##STR00212## ##STR00213## ##STR00214## ##STR00215## ##STR00216## ##STR00217## ##STR00218## ##STR00219## ##STR00220## ##STR00221## ##STR00222## ##STR00223## ##STR00224## ##STR00225## ##STR00226## ##STR00227## ##STR00228## ##STR00229## ##STR00230## ##STR00231## ##STR00232##

3. The method according to claim 1, wherein the compound is formulated as liposomes or lipid nanoparticles.

4. The method according to claim 1, wherein the patient is a human patient.

5. A cultivated hepatocyte for treatment of liver failure and/or for treatment of impaired liver function and/or for blood purification, characterized in that the hepatocyte contains a compound which is an inhibitor of the activity of MKK4, wherein said MKK4 encoded by SEQ ID NO: 1204 and the compound is not SP600125, myricitine, PD98059, genistein, or ZM 336372.

6. A medicament comprising the cultivated hepatocyte of claim 5.

7. The cultivated hepatocyte of claim 5, wherein the hepatocyte is arranged in a vessel having an entry port for entry of blood of a patient and an exit port for recirculating the blood to the patient.

8. The cultivated hepatocyte of claim 5, wherein the compound is one or more of the compounds of claim 2.