Top ▲

mitogen-activated protein kinase 10

Click here for help

Target id: 1498

Nomenclature: mitogen-activated protein kinase 10

Abbreviated Name: JNK3

Family: JNK subfamily

Contents:

Gene and Protein Information Click here for help
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human - 464 4q21.3 MAPK10 mitogen-activated protein kinase 10
Mouse - 494 5 E5 Mapk10 mitogen-activated protein kinase 10
Rat - 464 14p22 Mapk10 mitogen activated protein kinase 10
Previous and Unofficial Names Click here for help
c-Jun N-terminal kinase 3 | JNK3A | MAP kinase 10 | p54-beta | p54bSAPK | PRKM10 | SAPK1B | SAPK-beta | SAPKC | Serk2 | stress-activated protein kinase JNK3 | Stress activated protein kinase beta
Database Links Click here for help
Alphafold P53779 (Hs), E9QN59 (Mm), P49187 (Rn)
BRENDA 2.7.11.24
ChEMBL Target CHEMBL2637 (Hs), CHEMBL4092 (Rn)
Ensembl Gene ENSG00000109339 (Hs), ENSMUSG00000046709 (Mm), ENSRNOG00000002079 (Rn)
Entrez Gene 5602 (Hs), 26414 (Mm), 25272 (Rn)
Human Protein Atlas ENSG00000109339 (Hs)
KEGG Enzyme 2.7.11.24
KEGG Gene hsa:5602 (Hs), mmu:26414 (Mm), rno:25272 (Rn)
OMIM 602897 (Hs)
Orphanet ORPHA248276 (Hs)
Pharos P53779 (Hs)
RefSeq Nucleotide NM_002753 (Hs), NM_001081567 (Mm), NM_001270556 (Rn)
RefSeq Protein NP_002744 (Hs), NP_001075036 (Mm), NP_001257485 (Rn)
SynPHARM 83982 (in complex with JNK inhibitor 9l)
78580 (in complex with SP600125)
84911 (in complex with tanzisertib)
UniProtKB P53779 (Hs), E9QN59 (Mm), P49187 (Rn)
Wikipedia MAPK10 (Hs)
Selected 3D Structures Click here for help
Image of receptor 3D structure from RCSB PDB
Description:  Crystal Structure of JNK3 in Complex with JIP1 Peptide
PDB Id:  4H39
Resolution:  1.99Å
Species:  Human
References:  9
Enzyme Reaction Click here for help
EC Number: 2.7.11.24

Download all structure-activity data for this target as a CSV file go icon to follow link

Inhibitors
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
pamapimod Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibition 7.7 pKd 7
⤷ pKd 7.7 (Kd 1.9x10-8 M) [7]
Description: In a biochemical assay.
JNK inhibitor VIII Small molecule or natural product Click here for species-specific activity table Hs Inhibition 7.3 pKi 15
⤷ pKi 7.3 (Ki 5.2x10-8 M) [15]
JNK-IN-8 Small molecule or natural product Primary target of this compound Click here for species-specific activity table Hs Inhibition 9.0 pIC50 18
⤷ pIC50 9.0 (IC50 1x10-9 M) [18]
tanzisertib Small molecule or natural product Click here for species-specific activity table Immunopharmacology Ligand Hs Inhibition 8.2 pIC50 12
⤷ pIC50 8.2 (IC50 6x10-9 M) [12]
J30-8 Small molecule or natural product Primary target of this compound Hs Inhibition 7.4 pIC50 5
⤷ pIC50 7.4 (IC50 4x10-8 M) [5]
JNK inhibitor V Small molecule or natural product Primary target of this compound Hs Inhibition 7.2 pIC50
⤷ pIC50 7.2 (IC50 7x10-8 M)
compound 25c [PMID: 36649216] Small molecule or natural product Click here for species-specific activity table Hs Inhibition 7.1 pIC50 14
⤷ pIC50 7.1 (IC50 8.52x10-8 M) [14]
SP600125 Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibition 7.1 pIC50 2
⤷ pIC50 7.1 (IC50 9x10-8 M) [2]
brimapitide Peptide Immunopharmacology Ligand Hs Inhibition ~7.0 pIC50 3
⤷ pIC50 ~7.0 (IC50 ~1x10-7 M) [3]
Description: Alphascreen kinase assay result
compound 20 [PMID: 30998356] Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 7.0 pIC50 13
⤷ pIC50 7.0 (IC50 1.07x10-7 M) [13]
Description: Measuring in vitro enzyme inhibitory activity.
JNK inhibitor 9l Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 6.8 pIC50 8
⤷ pIC50 6.8 (IC50 1.48x10-7 M) [8]
JNK inhibitor IX Small molecule or natural product Primary target of this compound Click here for species-specific activity table Immunopharmacology Ligand Hs Inhibition 6.7 pIC50
⤷ pIC50 6.7 (IC50 1.995x10-7 M)
BOS172722 Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 6.6 pIC50 17
⤷ pIC50 6.6 (IC50 2.42x10-7 M) [17]
GNE-3511 Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 6.4 pIC50 10
⤷ pIC50 6.4 (IC50 3.64x10-7 M) [10]
compound 11 [PMID: 26431428] Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 5.7 pIC50 11
⤷ pIC50 5.7 (IC50 2.1x10-6 M) [11]
Inhibitor Comments
We have mapped brimapitide to JNK3, as this appears to be the isozyme used in [3], but it is likely to inhibit kinase activity of all JNK enzymes.
DiscoveRx KINOMEscan® screen Click here for help
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: 4,16
Key to terms and symbols Click column headers to sort
Target used in screen: JNK3
Ligand Sp. Type Action Value Parameter
lestaurtinib Small molecule or natural product Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 7.9 pKd
SB203580 Small molecule or natural product Immunopharmacology Ligand Hs Inhibitor Inhibition 7.5 pKd
tamatinib Small molecule or natural product Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 7.4 pKd
KW-2449 Small molecule or natural product Hs Inhibitor Inhibition 7.3 pKd
NVP-TAE684 Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 7.2 pKd
doramapimod Small molecule or natural product Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 7.0 pKd
staurosporine Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 7.0 pKd
GSK-1838705A Small molecule or natural product Hs Inhibitor Inhibition 6.9 pKd
fedratinib Small molecule or natural product Approved drug Ligand has a PDB structure Hs Inhibitor Inhibition 6.7 pKd
JNJ-28312141 Small molecule or natural product Hs Inhibitor Inhibition 6.6 pKd
Displaying the top 10 most potent ligands  View all ligands in screen »
EMD Millipore KinaseProfilerTM screen/Reaction Biology Kinase HotspotSM screen Click here for help
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
Key to terms and symbols Click column headers to sort
Target used in screen: JNK3/JNK3
Ligand Sp. Type Action % Activity remaining at 0.5µM % Activity remaining at 1µM % Activity remaining at 10µM
JNK inhibitor VIII Small molecule or natural product Hs Inhibitor Inhibition 51.5 -2.0 -2.0
PDK1/Akt/Flt dual pathway inhibitor Small molecule or natural product Hs Inhibitor Inhibition 55.0 112.0 100.0
fascaplysin Small molecule or natural product Hs Inhibitor Inhibition 71.6 71.0 62.0
NU-7026 Small molecule or natural product Hs Inhibitor Inhibition 73.8 98.0 70.0
DNA-PK inhibitor V Small molecule or natural product Hs Inhibitor Inhibition 75.3 83.0 53.0
diacylglycerol kinase inhibitor II Small molecule or natural product Hs Inhibitor Inhibition 76.2 98.0 54.0
DNA-PK inhibitor III Small molecule or natural product Hs Inhibitor Inhibition 78.4 88.0 85.0
DMBI Small molecule or natural product Hs Inhibitor Inhibition 82.9 110.0 106.0
GSK-3 inhibitor X Small molecule or natural product Hs Inhibitor Inhibition 83.0 77.0 61.0
EGFR inhibitor Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 83.4 82.0 52.0
Displaying the top 10 most potent ligands  View all ligands in screen »
Immuno Process Associations
Immuno Process:  Immune regulation
Immuno Process:  Cellular signalling
Clinically-Relevant Mutations and Pathophysiology Click here for help
Disease:  Lennox-Gastaut syndrome
Disease Ontology: DOID:0050561
Orphanet: ORPHA2382

References

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 USA, 98 (24): 13681-6. [PMID:11717429]

3. Bonny C. (2011) Cell-permeable peptide inhibitors of the JNK signal transduction pathway. Patent number: US8080517 B2. Assignee: Xigen Sa. Priority date: 12/09/2005. Publication date: 20/12/2011.

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. Dou X, Huang H, Li Y, Jiang L, Wang Y, Jin H, Jiao N, Zhang L, Zhang L, Liu Z. (2019) Multistage Screening Reveals 3-Substituted Indolin-2-one Derivatives as Novel and Isoform-Selective c-Jun N-terminal Kinase 3 (JNK3) Inhibitors: Implications to Drug Discovery for Potential Treatment of Neurodegenerative Diseases. J Med Chem, 62 (14): 6645-6664. [PMID:31268308]

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. Laughlin JD, Nwachukwu JC, Figuera-Losada M, Cherry L, Nettles KW, LoGrasso PV. (2012) Structural mechanisms of allostery and autoinhibition in JNK family kinases. Structure, 20 (12): 2174-84. [PMID:23142346]

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. 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]

15. 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]

16. 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]

17. 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]

18. 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 10. Last modified on 06/06/2023. Accessed on 11/12/2024. IUPHAR/BPS Guide to PHARMACOLOGY, https://www.guidetomalariapharmacology.org/GRAC/ObjectDisplayForward?objectId=1498.