mitogen-activated protein kinase 9 | JNK subfamily | IUPHAR/BPS Guide to PHARMACOLOGY

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mitogen-activated protein kinase 9

target has curated data in GtoImmuPdb

Target id: 1497

Nomenclature: mitogen-activated protein kinase 9

Abbreviated Name: JNK2

Family: JNK subfamily

Gene and Protein Information
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human - 242 5q35 MAPK9 mitogen-activated protein kinase 9
Mouse - 423 11 B1.2 Mapk9 mitogen-activated protein kinase 9
Rat - 423 10 q22 Mapk9 mitogen-activated protein kinase 9
Previous and Unofficial Names
JNK-55 | c-Jun N-terminal kinase 2 | JNK/SAPK alpha | Jun kinase | MAP kinase 9 | PRKM9 | SAPK1A | SAPK-alpha | stress activated protein kinase alpha II | Stress-activated protein kinase 1a | stress-activated protein kinase JNK2
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:  Crystal Structure of JNK2
PDB Id:  3E7O
Resolution:  2.14Å
Species:  Human
References:  14
Image of receptor 3D structure from RCSB PDB
Description:  Crystal structure of JNK2 complexed with BIRB796
Ligand:  doramapimod
Resolution:  2.35Å
Species:  Human
References:  10
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 7.8 pKd 7
pKd 7.8 (Kd 1.6x10-8 M) [7]
Description: In a biochemical assay.
JNK inhibitor VIII Hs Inhibition 8.4 pKi 16
pKi 8.4 (Ki 4x10-9 M) [16]
tanzisertib Hs Inhibition 8.1 pIC50 11
pIC50 8.1 (IC50 7x10-9 M) [11]
JNK-IN-8 Hs Inhibition 7.7 pIC50 19
pIC50 7.7 (IC50 1.87x10-8 M) [19]
SP600125 Hs Inhibition 7.4 pIC50 3
pIC50 7.4 (IC50 4x10-8 M) [3]
RGB-286638 Hs Inhibition 7.4 pIC50 4
pIC50 7.4 (IC50 4x10-8 M) [4]
compound 20 [PMID: 30998356] Hs Inhibition 7.2 pIC50 12
pIC50 7.2 (IC50 5.9x10-8 M) [12]
Description: Measuring in vitro enzyme inhibitory activity.
JNK inhibitor IX Hs Inhibition 6.5 pIC50 2
pIC50 6.5 (IC50 3.162x10-7 M) [2]
DiscoveRx KINOMEscan® screen
A screen of 72 inhibitors against 456 human kinases. Quantitative data were derived using DiscoveRx KINOMEscan® platform.
Reference: 5,17

Key to terms and symbols Click column headers to sort
Target used in screen: JNK2
Ligand Sp. Type Action Value Parameter
doramapimod Hs Inhibitor Inhibition 8.1 pKd
tamatinib Hs Inhibitor Inhibition 7.3 pKd
AST-487 Hs Inhibitor Inhibition 7.3 pKd
SB203580 Hs Inhibitor Inhibition 6.9 pKd
KW-2449 Hs Inhibitor Inhibition 6.6 pKd
fedratinib Hs Inhibitor Inhibition 6.6 pKd
linifanib Hs Inhibitor Inhibition 6.6 pKd
NVP-TAE684 Hs Inhibitor Inhibition 6.6 pKd
lestaurtinib Hs Inhibitor Inhibition 6.5 pKd
GSK-1838705A Hs Inhibitor Inhibition 6.3 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: JNK2α2/JNK2
Ligand Sp. Type Action % Activity remaining at 0.5µM % Activity remaining at 1µM % Activity remaining at 10µM
p38 MAP kinase inhibitor Hs Inhibitor Inhibition 6.1 7.0 -10.0
JNK inhibitor VIII Hs Inhibitor Inhibition 6.4 -1.0 -11.0
K-252a Hs Inhibitor Inhibition 12.4 5.0 -11.0
p38 MAP kinase inhibitor III Hs Inhibitor Inhibition 31.1 39.0 -6.0
JAK inhibitor I Hs Inhibitor Inhibition 31.1 64.0 17.0
JNK inhibitor IX Hs Inhibitor Inhibition 33.9 58.0 74.0
SP600125 Hs Inhibitor Inhibition 36.4 26.0 -6.0
indirubin derivative E804 Hs Inhibitor Inhibition 44.3 43.0 30.0
PD 169316 Hs Inhibitor Inhibition 45.5 68.0 59.0
PKR inhibitor Hs Inhibitor Inhibition 45.8 71.0 16.0
Displaying the top 10 most potent ligands  View all ligands in screen »
Immunopharmacology Comments
Experimental evidence suggests that JNK2 is important in T-cell differentiation [8,13,15,18]. Signalling through JNK2, but not JNK1 has been associated with a loss of Treg cell function and an increase in pathogenic CD4+ T effector cell function, and the exacerbation of asthma-like immunopathology in mice [9].
Immuno Process Associations
Immuno Process:  Immune regulation
GO Annotations:  Associated to 1 GO processes
GO:0038095 Fc-epsilon receptor signaling pathway TAS
Immuno Process:  Cellular signalling
GO Annotations:  Associated to 3 GO processes
GO:0031396 regulation of protein ubiquitination IMP
GO:0038095 Fc-epsilon receptor signaling pathway TAS
click arrow to show/hide IEA associations
GO:0031398 positive regulation of protein ubiquitination IEA
Immuno Process:  Chemotaxis & migration
GO Annotations:  Associated to 1 GO processes
GO:0032722 positive regulation of chemokine production IMP
Immuno Process:  Cytokine production & signalling
GO Annotations:  Associated to 3 GO processes
GO:0032722 positive regulation of chemokine production IMP
GO:0071347 cellular response to interleukin-1 IEP
GO:0071356 cellular response to tumor necrosis factor IEP


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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. Angell RM, Atkinson FL, Brown MJ, Chuang TT, Christopher JA, Cichy-Knight M, Dunn AK, Hightower KE, Malkakorpi S, Musgrave JR et al.. (2007) N-(3-Cyano-4,5,6,7-tetrahydro-1-benzothien-2-yl)amides as potent, selective, inhibitors of JNK2 and JNK3. Bioorg. Med. Chem. Lett., 17 (5): 1296-301. [PMID:17194588]

3. 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]

4. Cirstea D, Hideshima T, Santo L, Eda H, Mishima Y, Nemani N, Hu Y, Mimura N, Cottini F, Gorgun G et al.. (2013) Small-molecule multi-targeted kinase inhibitor RGB-286638 triggers P53-dependent and -independent anti-multiple myeloma activity through inhibition of transcriptional CDKs. Leukemia, 27 (12): 2366-75. [PMID:23807770]

5. 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]

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. Jang WY, Lee JY, Lee ST, Jun do Y, Kim YH. (2014) Inhibition of JNK2 and JNK3 by JNK inhibitor IX induces prometaphase arrest-dependent apoptotic cell death in human Jurkat T cells. Biochem. Biophys. Res. Commun., 452 (3): 845-51. [PMID:25218503]

9. Joetham A, Schedel M, Takeda K, Jia Y, Ashino S, Dakhama A, Lluis A, Okamoto M, Gelfand EW. (2014) JNK2 regulates the functional plasticity of naturally occurring T regulatory cells and the enhancement of lung allergic responses. J. Immunol., 193 (5): 2238-47. [PMID:25070841]

10. Kuglstatter A, Ghate M, Tsing S, Villaseñor AG, Shaw D, Barnett JW, Browner MF. (2010) X-ray crystal structure of JNK2 complexed with the p38alpha inhibitor BIRB796: insights into the rational design of DFG-out binding MAP kinase inhibitors. Bioorg. Med. Chem. Lett., 20 (17): 5217-20. [PMID:20655210]

11. 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]

12. 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]

13. Sabapathy K, Hu Y, Kallunki T, Schreiber M, David JP, Jochum W, Wagner EF, Karin M. (1999) JNK2 is required for efficient T-cell activation and apoptosis but not for normal lymphocyte development. Curr. Biol., 9 (3): 116-25. [PMID:10021384]

14. Shaw D, Wang SM, Villaseñor AG, Tsing S, Walter D, Browner MF, Barnett J, Kuglstatter A. (2008) The crystal structure of JNK2 reveals conformational flexibility in the MAP kinase insert and indicates its involvement in the regulation of catalytic activity. J. Mol. Biol., 383 (4): 885-93. [PMID:18801372]

15. Su B, Jacinto E, Hibi M, Kallunki T, Karin M, Ben-Neriah Y. (1994) JNK is involved in signal integration during costimulation of T lymphocytes. Cell, 77 (5): 727-36. [PMID:8205621]

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. Yang DD, Conze D, Whitmarsh AJ, Barrett T, Davis RJ, Rincón M, Flavell RA. (1998) Differentiation of CD4+ T cells to Th1 cells requires MAP kinase JNK2. Immunity, 9 (4): 575-85. [PMID:9806643]

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]

How to cite this page

JNK subfamily: mitogen-activated protein kinase 9. Last modified on 30/10/2019. Accessed on 29/09/2020. IUPHAR/BPS Guide to PHARMACOLOGY,