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target has curated data in GtoImmuPdb
Target id: 1496
Nomenclature: mitogen-activated protein kinase 8
Abbreviated Name: JNK1
Family: JNK subfamily
Gene and Protein Information ![]() |
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Species | TM | AA | Chromosomal Location | Gene Symbol | Gene Name | Reference |
Human | - | 427 | 10q11.22 | MAPK8 | mitogen-activated protein kinase 8 | |
Mouse | - | 384 | 14 B | Mapk8 | mitogen-activated protein kinase 8 | |
Rat | - | 411 | 16p16 | Mapk8 | mitogen-activated protein kinase 8 |
Database Links ![]() |
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Alphafold | P45983 (Hs), Q91Y86 (Mm), P49185 (Rn) |
BRENDA | 2.7.11.24 |
ChEMBL Target | CHEMBL2276 (Hs), CHEMBL1795174 (Mm), CHEMBL5718 (Rn) |
Ensembl Gene | ENSG00000107643 (Hs), ENSMUSG00000021936 (Mm), ENSRNOG00000020155 (Rn) |
Entrez Gene | 5599 (Hs), 26419 (Mm), 116554 (Rn) |
Human Protein Atlas | ENSG00000107643 (Hs) |
KEGG Enzyme | 2.7.11.24 |
KEGG Gene | hsa:5599 (Hs), mmu:26419 (Mm), rno:116554 (Rn) |
OMIM | 601158 (Hs) |
Pharos | P45983 (Hs) |
RefSeq Nucleotide | NM_002750 (Hs), NM_016700 (Mm), NM_053829 (Rn) |
RefSeq Protein | NP_002741 (Hs), NP_057909 (Mm), NP_446281 (Rn) |
SynPHARM | 78578 (in complex with SP600125) |
UniProtKB | P45983 (Hs), Q91Y86 (Mm), P49185 (Rn) |
Wikipedia | MAPK8 (Hs) |
Selected 3D Structures ![]() |
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Enzyme Reaction ![]() |
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Download all structure-activity data for this target as a CSV file
Inhibitors | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Key to terms and symbols | View all chemical structures | Click column headers to sort | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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DiscoveRx KINOMEscan® screen ![]() |
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A screen of 72 inhibitors against 456 human kinases. Quantitative data were derived using DiscoveRx KINOMEscan® platform. http://www.discoverx.com/services/drug-discovery-development-services/kinase-profiling/kinomescan Reference: 4,17 |
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Target used in screen: JNK1 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Displaying the top 10 most potent ligands View all ligands in screen » |
EMD Millipore KinaseProfilerTM screen/Reaction Biology Kinase HotspotSM screen ![]() |
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A screen profiling 158 kinase inhibitors (Calbiochem Protein Kinase Inhibitor Library I and II, catalogue numbers 539744 and 539745) for their inhibitory activity at 1µM and 10µM against 234 human recombinant kinases using the EMD Millipore KinaseProfilerTM service. A screen profiling the inhibitory activity of 178 commercially available kinase inhibitors at 0.5µM against a panel of 300 recombinant protein kinases using the Reaction Biology Corporation Kinase HotspotSM platform. http://www.millipore.com/techpublications/tech1/pf3036 http://www.reactionbiology.com/webapps/main/pages/kinase.aspx Reference: 1,6 |
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Target used in screen: JNK1α1/JNK1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Displaying the top 10 most potent ligands View all ligands in screen » |
Immunopharmacology Comments |
By regulating AP-1 transcriptional activity in response to cytokine activation, JNK1 contributes to the production of immunomodulators such as RANTES, IL-8 and GM-CSF . |
Immuno Process Associations | ||
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1. Anastassiadis T, Deacon SW, Devarajan K, Ma H, Peterson JR. (2011) Comprehensive assay of kinase catalytic activity reveals features of kinase inhibitor selectivity. Nat Biotechnol, 29 (11): 1039-45. [PMID:22037377]
2. Bennett BL, Sasaki DT, Murray BW, O'Leary EC, Sakata ST, Xu W, Leisten JC, Motiwala A, Pierce S, Satoh Y et al.. (2001) SP600125, an anthrapyrazolone inhibitor of Jun N-terminal kinase. Proc Natl Acad Sci USA, 98 (24): 13681-6. [PMID:11717429]
3. Chamberlain SD, Redman AM, Wilson JW, Deanda F, Shotwell JB, Gerding R, Lei H, Yang B, Stevens KL, Hassell AM et al.. (2009) Optimization of 4,6-bis-anilino-1H-pyrrolo[2,3-d]pyrimidine IGF-1R tyrosine kinase inhibitors towards JNK selectivity. Bioorg Med Chem Lett, 19 (2): 360-4. [PMID:19071018]
4. Davis MI, Hunt JP, Herrgard S, Ciceri P, Wodicka LM, Pallares G, Hocker M, Treiber DK, Zarrinkar PP. (2011) Comprehensive analysis of kinase inhibitor selectivity. Nat Biotechnol, 29 (11): 1046-51. [PMID:22037378]
5. De SK, Stebbins JL, Chen LH, Riel-Mehan M, Machleidt T, Dahl R, Yuan H, Emdadi A, Barile E, Chen V et al.. (2009) Design, synthesis, and structure-activity relationship of substrate competitive, selective, and in vivo active triazole and thiadiazole inhibitors of the c-Jun N-terminal kinase. J Med Chem, 52 (7): 1943-52. [PMID:19271755]
6. Gao Y, Davies SP, Augustin M, Woodward A, Patel UA, Kovelman R, Harvey KJ. (2013) A broad activity screen in support of a chemogenomic map for kinase signalling research and drug discovery. Biochem J, 451 (2): 313-28. [PMID:23398362]
7. Goldstein DM, Soth M, Gabriel T, Dewdney N, Kuglstatter A, Arzeno H, Chen J, Bingenheimer W, Dalrymple SA, Dunn J et al.. (2011) Discovery of 6-(2,4-difluorophenoxy)-2-[3-hydroxy-1-(2-hydroxyethyl)propylamino]-8-methyl-8H-pyrido[2,3-d]pyrimidin-7-one (pamapimod) and 6-(2,4-difluorophenoxy)-8-methyl-2-(tetrahydro-2H-pyran-4-ylamino)pyrido[2,3-d]pyrimidin-7(8H)-one (R1487) as orally bioavailable and highly selective inhibitors of p38
8. Kamenecka T, Jiang R, Song X, Duckett D, Chen W, Ling YY, Habel J, Laughlin JD, Chambers J, Figuera-Losada M et al.. (2010) Synthesis, biological evaluation, X-ray structure, and pharmacokinetics of aminopyrimidine c-jun-N-terminal kinase (JNK) inhibitors. J Med Chem, 53 (1): 419-31. [PMID:19947601]
9. Li B, Cociorva OM, Nomanbhoy T, Weissig H, Li Q, Nakamura K, Liyanage M, Zhang MC, Shih AY, Aban A et al.. (2013) Hit-to-lead optimization and kinase selectivity of imidazo[1,2-a]quinoxalin-4-amine derived JNK1 inhibitors. Bioorg Med Chem Lett, 23 (18): 5217-22. [PMID:23916259]
10. Lu W, Liu Y, Gao Y, Geng Q, Gurbani D, Li L, Ficarro SB, Meyer CJ, Sinha D, You I et al.. (2023) Development of a Covalent Inhibitor of c-Jun N-Terminal Protein Kinase (JNK) 2/3 with Selectivity over JNK1. J Med Chem, 66 (5): 3356-3371. [PMID:36826833]
11. Patel S, Cohen F, Dean BJ, De La Torre K, Deshmukh G, Estrada AA, Ghosh AS, Gibbons P, Gustafson A, Huestis MP et al.. (2015) Discovery of dual leucine zipper kinase (DLK, MAP3K12) inhibitors with activity in neurodegeneration models. J Med Chem, 58 (1): 401-18. [PMID:25341110]
12. Patel S, Harris SF, Gibbons P, Deshmukh G, Gustafson A, Kellar T, Lin H, Liu X, Liu Y, Liu Y et al.. (2015) Scaffold-Hopping and Structure-Based Discovery of Potent, Selective, And Brain Penetrant N-(1H-Pyrazol-3-yl)pyridin-2-amine Inhibitors of Dual Leucine Zipper Kinase (DLK, MAP3K12). J Med Chem, 58 (20): 8182-99. [PMID:26431428]
13. Plantevin Krenitsky V, Nadolny L, Delgado M, Ayala L, Clareen SS, Hilgraf R, Albers R, Hegde S, D'Sidocky N, Sapienza J et al.. (2012) Discovery of CC-930, an orally active anti-fibrotic JNK inhibitor. Bioorg Med Chem Lett, 22 (3): 1433-8. [PMID:22244937]
14. Riggs JR, Elsner J, Cashion D, Robinson D, Tehrani L, Nagy M, Fultz KE, Krishna Narla R, Peng X, Tran T et al.. (2019) Design and Optimization Leading to an Orally Active TTK Protein Kinase Inhibitor with Robust Single Agent Efficacy. J Med Chem, 62 (9): 4401-4410. [PMID:30998356]
15. Shuai W, Bu F, Zhu Y, Wu Y, Xiao H, Pan X, Zhang J, Sun Q, Wang G, Ouyang L. (2023) Discovery of Novel Indazole Chemotypes as Isoform-Selective JNK3 Inhibitors for the Treatment of Parkinson's Disease. J Med Chem, 66 (2): 1273-1300. [PMID:36649216]
16. Szczepankiewicz BG, Kosogof C, Nelson LT, Liu G, Liu B, Zhao H, Serby MD, Xin Z, Liu M, Gum RJ et al.. (2006) Aminopyridine-based c-Jun N-terminal kinase inhibitors with cellular activity and minimal cross-kinase activity. J Med Chem, 49 (12): 3563-80. [PMID:16759099]
17. Wodicka LM, Ciceri P, Davis MI, Hunt JP, Floyd M, Salerno S, Hua XH, Ford JM, Armstrong RC, Zarrinkar PP et al.. (2010) Activation state-dependent binding of small molecule kinase inhibitors: structural insights from biochemistry. Chem Biol, 17 (11): 1241-9. [PMID:21095574]
18. Woodward HL, Innocenti P, Cheung KJ, Hayes A, Roberts J, Henley AT, Faisal A, Mak GW, Box G, Westwood IM et al.. (2018) Introduction of a Methyl Group Curbs Metabolism of Pyrido[3,4- d]pyrimidine Monopolar Spindle 1 (MPS1) Inhibitors and Enables the Discovery of the Phase 1 Clinical Candidate N2-(2-Ethoxy-4-(4-methyl-4 H-1,2,4-triazol-3-yl)phenyl)-6-methyl- N8-neopentylpyrido[3,4- d]pyrimidine-2,8-diamine (BOS172722). J Med Chem, 61 (18): 8226-8240. [PMID:30199249]
19. Zhang T, Inesta-Vaquera F, Niepel M, Zhang J, Ficarro SB, Machleidt T, Xie T, Marto JA, Kim N, Sim T et al.. (2012) Discovery of potent and selective covalent inhibitors of JNK. Chem Biol, 19 (1): 140-54. [PMID:22284361]
JNK subfamily: mitogen-activated protein kinase 8. Last modified on 06/06/2023. Accessed on 29/08/2024. IUPHAR/BPS Guide to PHARMACOLOGY, https://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=1496.