mitogen-activated protein kinase 10 | JNK subfamily | IUPHAR/BPS Guide to PHARMACOLOGY

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mitogen-activated protein kinase 10

Target not currently curated in GtoImmuPdb

Target id: 1498

Nomenclature: mitogen-activated protein kinase 10

Abbreviated Name: JNK3

Family: JNK subfamily

Annotation status:  image of an orange circle Annotated and awaiting review. Please contact us if you can help with reviewing.  » Email us

Gene and Protein Information
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human - 422 4q22-q23 MAPK10 mitogen-activated protein kinase 10
Mouse - 464 5 E4 Mapk10 mitogen-activated protein kinase 10
Rat - 464 14p22 Mapk10 mitogen activated protein kinase 10
Previous and Unofficial Names
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
BRENDA
ChEMBL Target
Ensembl Gene
Entrez Gene
Human Protein Atlas
KEGG Enzyme
KEGG Gene
OMIM
Orphanet
RefSeq Nucleotide
RefSeq Protein
SynPHARM
UniProtKB
Wikipedia
Selected 3D Structures
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
EC Number: 2.7.11.24

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
Ligand Sp. Action Value Parameter Reference
pamapimod Hs Inhibition 7.7 pKd 7
pKd 7.7 (Kd 1.9x10-8 M) [7]
Description: In a biochemical assay.
JNK inhibitor VIII Hs Inhibition 7.3 pKi 14
pKi 7.3 (Ki 5.2x10-8 M) [14]
JNK-IN-8 Hs Inhibition 9.0 pIC50 16
pIC50 9.0 (IC50 1x10-9 M) [16]
tanzisertib Hs Inhibition 8.2 pIC50 12
pIC50 8.2 (IC50 6x10-9 M) [12]
J30-8 Hs Inhibition 7.4 pIC50 5
pIC50 7.4 (IC50 4x10-8 M) [5]
JNK inhibitor V Hs Inhibition 7.2 pIC50
pIC50 7.2 (IC50 7x10-8 M)
SP600125 Hs Inhibition 7.1 pIC50 2
pIC50 7.1 (IC50 9x10-8 M) [2]
brimapitide Hs Inhibition ~7.0 pIC50 3
pIC50 ~7.0 (IC50 ~1x10-7 M) [3]
Description: Alphascreen kinase assay result
compound 20 [PMID: 30998356] 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 Hs Inhibition 6.8 pIC50 8
pIC50 6.8 (IC50 1.48x10-7 M) [8]
JNK inhibitor IX Hs Inhibition 6.7 pIC50
pIC50 6.7 (IC50 1.995x10-7 M)
GNE-3511 Hs Inhibition 6.4 pIC50 10
pIC50 6.4 (IC50 3.64x10-7 M) [10]
compound 11 [PMID: 26431428] 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
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: 4,15

Key to terms and symbols Click column headers to sort
Target used in screen: JNK3
Ligand Sp. Type Action Value Parameter
lestaurtinib Hs Inhibitor Inhibition 7.9 pKd
SB203580 Hs Inhibitor Inhibition 7.5 pKd
tamatinib Hs Inhibitor Inhibition 7.4 pKd
KW-2449 Hs Inhibitor Inhibition 7.3 pKd
NVP-TAE684 Hs Inhibitor Inhibition 7.2 pKd
doramapimod Hs Inhibitor Inhibition 7.0 pKd
staurosporine Hs Inhibitor Inhibition 7.0 pKd
GSK-1838705A Hs Inhibitor Inhibition 6.9 pKd
fedratinib Hs Inhibitor Inhibition 6.7 pKd
JNJ-28312141 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
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 Hs Inhibitor Inhibition 51.5 -2.0 -2.0
PDK1/Akt/Flt dual pathway inhibitor Hs Inhibitor Inhibition 55.0 112.0 100.0
fascaplysin Hs Inhibitor Inhibition 71.6 71.0 62.0
NU-7026 Hs Inhibitor Inhibition 73.8 98.0 70.0
DNA-PK inhibitor V Hs Inhibitor Inhibition 75.3 83.0 53.0
diacylglycerol kinase inhibitor II Hs Inhibitor Inhibition 76.2 98.0 54.0
DNA-PK inhibitor III Hs Inhibitor Inhibition 78.4 88.0 85.0
DMBI Hs Inhibitor Inhibition 82.9 110.0 106.0
GSK-3 inhibitor X Hs Inhibitor Inhibition 83.0 77.0 61.0
EGFR inhibitor Hs Inhibitor Inhibition 83.4 82.0 52.0
Displaying the top 10 most potent ligands  View all ligands in screen »
Clinically-Relevant Mutations and Pathophysiology
Disease:  Lennox-Gastaut syndrome
Disease Ontology: DOID:0050561
Orphanet: ORPHA2382

References

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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. U.S.A., 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. 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]

How to cite this page

JNK subfamily: mitogen-activated protein kinase 10. Last modified on 17/07/2019. Accessed on 18/09/2019. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=1498.