mitogen-activated protein kinase 8 | JNK subfamily | IUPHAR/BPS Guide to PHARMACOLOGY

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mitogen-activated protein kinase 8

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
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human - 384 10q11 MAPK8 mitogen-activated protein kinase 8
Mouse - 384 14 B Mapk8 mitogen-activated protein kinase 8
Rat - 427 16p16 Mapk8 mitogen-activated protein kinase 8
Previous and Unofficial Names
c-jun NH2-terminal kinase | c-Jun N-terminal kinase 1 | JNK | JNK-46 | MAP kinase 8 | PRKM8 | SAPK gamma | SAPK1C | Stress-activated protein kinase 1c | stress-activated protein kinase JNK1
Database Links
ChEMBL Target
Ensembl Gene
Entrez Gene
Human Protein Atlas
KEGG Enzyme
RefSeq Nucleotide
RefSeq Protein
Selected 3D Structures
Image of receptor 3D structure from RCSB PDB
Description:  Jnk1 complexed with a bis-anilino-pyrrolopyrimidine inhibitor.
Resolution:  1.8Å
Species:  Human
References:  3
Enzyme Reaction
EC Number:

Download all structure-activity data for this target as a CSV file

Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
pamapimod Hs Inhibition 6.7 pKd 7
pKd 6.7 (Kd 1.9x10-7 M) [7]
Description: In a biochemical assay.
JNK inhibitor VIII Hs Inhibition 8.7 pKi 14
pKi 8.7 (Ki 2x10-9 M) [14]
JNK-IN-8 Hs Inhibition 8.3 pIC50 16
pIC50 8.3 (IC50 4.7x10-9 M) [16]
compound 20 [PMID: 30998356] Hs Inhibition 7.5 pIC50 13
pIC50 7.5 (IC50 3.2x10-8 M) [13]
Description: Measuring in vitro enzyme inhibitory activity.
SP600125 Hs Inhibition 7.4 pIC50 2
pIC50 7.4 (IC50 4x10-8 M) [2]
tanzisertib Hs Inhibition 7.2 pIC50 12
pIC50 7.2 (IC50 6.1x10-8 M) [12]
compound 35 [PMID: 23916259] Hs Inhibition 7.0 pIC50 9
pIC50 7.0 (IC50 9.2x10-8 M) [9]
JNK inhibitor 9l Hs Inhibition 7.0 pIC50 8
pIC50 7.0 (IC50 9.9x10-8 M) [8]
GNE-3511 Hs Inhibition 6.9 pIC50 10
pIC50 6.9 (IC50 1.29x10-7 M) [10]
SU-3327 Hs Inhibition 6.2 pIC50 5
pIC50 6.2 (IC50 7x10-7 M) [5]
Description: Biochemical inhibition in a LanthaScreen kinase activity assay.
compound 11 [PMID: 26431428] Hs Inhibition 6.0 pIC50 11
pIC50 6.0 (IC50 1.004x10-6 M) [11]
DiscoveRx KINOMEscan® screen
A screen of 72 inhibitors against 456 human kinases. Quantitative data were derived using DiscoveRx KINOMEscan® platform.
Reference: 4,15

Key to terms and symbols Click column headers to sort
Target used in screen: JNK1
Ligand Sp. Type Action Value Parameter
lestaurtinib Hs Inhibitor Inhibition 8.0 pKd
tamatinib Hs Inhibitor Inhibition 7.4 pKd
NVP-TAE684 Hs Inhibitor Inhibition 6.8 pKd
GSK-1838705A Hs Inhibitor Inhibition 6.7 pKd
staurosporine Hs Inhibitor Inhibition 6.7 pKd
fedratinib Hs Inhibitor Inhibition 6.6 pKd
nilotinib Hs Inhibitor Inhibition 6.3 pKd
AST-487 Hs Inhibitor Inhibition 6.3 pKd
KW-2449 Hs Inhibitor Inhibition 6.2 pKd
JNJ-28312141 Hs Inhibitor Inhibition 6.1 pKd
Displaying the top 10 most potent ligands  View all ligands in screen »
EMD Millipore KinaseProfilerTM screen/Reaction Biology Kinase HotspotSM screen
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.

Reference: 1,6

Key to terms and symbols Click column headers to sort
Target used in screen: JNK1α1/JNK1
Ligand Sp. Type Action % Activity remaining at 0.5µM % Activity remaining at 1µM % Activity remaining at 10µM
JNK inhibitor VIII Hs Inhibitor Inhibition 28.1 -16.0 -6.0
K-252a Hs Inhibitor Inhibition 28.8 -12.0 -20.0
Cdk2 inhibitor IV Hs Inhibitor Inhibition 51.1 44.0 -11.0
PD 174265 Hs Inhibitor Inhibition 73.7 94.0 76.0
JAK inhibitor I Hs Inhibitor Inhibition 73.7 32.0 9.0
aloisine Hs Inhibitor Inhibition 74.5 105.0 103.0
BAY 11-7082 Hs Inhibitor Inhibition 74.7 115.0 96.0
PDK1/Akt/Flt dual pathway inhibitor Hs Inhibitor Inhibition 78.3 114.0 83.0
Gö 6976 Hs Inhibitor Inhibition 78.7 88.0 31.0
Cdk1/2 inhibitor III Hs Inhibitor Inhibition 78.8 88.0 84.0
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
Immuno Process:  Immune regulation
GO Annotations:  Associated to 1 GO processes
GO:0038095 Fc-epsilon receptor signaling pathway TAS
Immuno Process:  Cytokine production & signalling
GO Annotations:  Associated to 2 GO processes
GO:0071345 cellular response to cytokine stimulus TAS
GO:0071347 cellular response to interleukin-1 IEP
Immuno Process:  Cellular signalling
GO Annotations:  Associated to 2 GO processes
GO:0031398 positive regulation of protein ubiquitination IMP
GO:0038095 Fc-epsilon receptor signaling pathway TAS
Immuno Process:  Inflammation
GO Annotations:  Associated to 1 GO processes
GO:0006954 inflammatory response IDA


Show »

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. U.S.A., 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 p38α mitogen-activated protein kinase. J. Med. Chem., 54 (7): 2255-65. [PMID:21375264]

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. 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]

11. 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]

12. 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]

13. 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]

14. 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]

15. 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]

16. 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]

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JNK subfamily: mitogen-activated protein kinase 8. Last modified on 28/02/2020. Accessed on 30/09/2020. IUPHAR/BPS Guide to PHARMACOLOGY,