Target Information

Target General Infomation
Target ID
T40097
Former ID
TTDC00102
Target Name
Mitogen-activated protein kinase 8
Gene Name
MAPK8
Synonyms
C-Jun N-terminal kinase 1; JNK-46; JNK1; Stress-activated protein kinase JNK1; MAPK8
Target Type
Clinical Trial
Disease Brain injury [ICD10: S09.90]
Neurodegenerative disease [ICD9: 330-337; ICD10: G30-G32]
Solid tumours [ICD9: 140-199, 210-229; ICD10: C00-D48]
Function
Responds to activation by environmental stress and pro- inflammatory cytokines by phosphorylating a number of transcription factors, primarily components of ap-1 such as c-jun and atf2 and thus regulates ap-1 transcriptional activity.
BioChemical Class
Kinase
Target Validation
T40097
UniProt ID
P45983
EC Number
EC 2.7.11.24
Sequence
MSRSKRDNNFYSVEIGDSTFTVLKRYQNLKPIGSGAQGIVCAAYDAILERNVAIKKLSRP
FQNQTHAKRAYRELVLMKCVNHKNIIGLLNVFTPQKSLEEFQDVYIVMELMDANLCQVIQ
MELDHERMSYLLYQMLCGIKHLHSAGIIHRDLKPSNIVVKSDCTLKILDFGLARTAGTSF
MMTPYVVTRYYRAPEVILGMGYKENVDLWSVGCIMGEMVCHKILFPGRDYIDQWNKVIEQ
LGTPCPEFMKKLQPTVRTYVENRPKYAGYSFEKLFPDVLFPADSEHNKLKASQARDLLSK
MLVIDASKRISVDEALQHPYINVWYDPSEAEAPPPKIPDKQLDEREHTIEEWKELIYKEV
MDLEERTKNGVIRGQPSPLGAAVINGSQHPSSSSSVNDVSSMSTDPTLASDTDSSLEAAA
GPLGCCR
Drugs and Mode of Action
Drug(s) CI-1040 Drug Info Phase 2 Discovery agent [1], [2]
NKP-1339 Drug Info Phase 1 Solid tumours [3]
Inhibitor 2,6-Dihydroanthra/1,9-Cd/Pyrazol-6-One Drug Info [4]
2-(2-(butylamino)pyrimidin-4-ylamino)benzoic acid Drug Info [5]
2-(2-(pentyloxy)pyrimidin-4-ylamino)benzoic acid Drug Info [5]
2-(2-(phenylamino)pyrimidin-4-ylamino)benzamide Drug Info [5]
2-(2-butoxypyrimidin-4-ylamino)benzoic acid Drug Info [5]
2-(2-phenoxypyrimidin-4-ylamino)benzoic acid Drug Info [5]
2-(2-propoxypyrimidin-4-ylamino)benzoic acid Drug Info [5]
2-(2-sec-butoxypyrimidin-4-ylamino)benzoic acid Drug Info [5]
4,5,6,7-tetrabromo-1H-benzo[d][1,2,3]triazole Drug Info [6]
aminopyridine deriv. 2 Drug Info [7]
AS-601245 Drug Info [8]
BISINDOLYLMALEIMIDE IX Drug Info [9]
CI-1040 Drug Info [9]
GF-109203 Drug Info [9]
JNK-IN-8 Drug Info [10]
KN-62 Drug Info [9]
KT-5720 Drug Info [9]
N-(4-amino-5-cyano-6-ethoxypyridin-2-yl)acetamide Drug Info [11]
N-(4-amino-5-cyano-6-phenylpyridin-2-yl)acetamide Drug Info [7]
N-(4-amino-6-butoxy-5-cyanopyridin-2-yl)acetamide Drug Info [7]
N-(6-ethoxypyridin-2-yl)acetamide Drug Info [7]
NKP-1339 Drug Info [12]
NM-PP1 Drug Info [8]
Phylomers Drug Info [12]
RO-316233 Drug Info [9]
Small molecule 32 Drug Info [12]
STAUROSPORINONE Drug Info [9]
Target Expression Profile (TEP) and Drug Resistance Mutation (DRM)
TEP EXP Info
Pathways
KEGG Pathway MAPK signaling pathway
ErbB signaling pathway
Ras signaling pathway
cAMP signaling pathway
FoxO signaling pathway
Sphingolipid signaling pathway
Protein processing in endoplasmic reticulum
Wnt signaling pathway
Osteoclast differentiation
Focal adhesion
Toll-like receptor signaling pathway
NOD-like receptor signaling pathway
RIG-I-like receptor signaling pathway
Fc epsilon RI signaling pathway
TNF signaling pathway
Neurotrophin signaling pathway
Retrograde endocannabinoid signaling
Dopaminergic synapse
Inflammatory mediator regulation of TRP channels
Insulin signaling pathway
GnRH signaling pathway
Progesterone-mediated oocyte maturation
Prolactin signaling pathway
Adipocytokine signaling pathway
Type II diabetes mellitus
Non-alcoholic fatty liver disease (NAFLD)
Epithelial cell signaling in Helicobacter pylori infection
Shigellosis
Salmonella infection
Pertussis
Chagas disease (American trypanosomiasis)
Toxoplasmosis
Tuberculosis
Hepatitis C
Hepatitis B
Influenza A
HTLV-I infection
Herpes simplex infection
Epstein-Barr virus infection
Pathways in cancer
Colorectal cancer
Pancreatic cancer
Choline metabolism in cancer
NetPath Pathway IL5 Signaling Pathway
TNFalpha Signaling Pathway
PANTHER Pathway Alzheimer disease-amyloid secretase pathway
Angiogenesis
Apoptosis signaling pathway
B cell activation
FAS signaling pathway
Integrin signalling pathway
Interferon-gamma signaling pathway
Oxidative stress response
PDGF signaling pathway
Parkinson disease
TGF-beta signaling pathway
T cell activation
Toll receptor signaling pathway
Ras Pathway
CCKR signaling map ST
Pathway Interaction Database Fc-epsilon receptor I signaling in mast cells
Endothelins
BCR signaling pathway
RhoA signaling pathway
Noncanonical Wnt signaling pathway
CD40/CD40L signaling
Signaling events mediated by Hepatocyte Growth Factor Receptor (c-Met)
Osteopontin-mediated events
Reelin signaling pathway
TRAIL signaling pathway
CDC42 signaling events
Signaling events regulated by Ret tyrosine kinase
Angiopoietin receptor Tie2-mediated signaling
FAS (CD95) signaling pathway
IL1-mediated signaling events
Role of Calcineurin-dependent NFAT signaling in lymphocytes
Glucocorticoid receptor regulatory network
IL2-mediated signaling events
Rapid glucocorticoid signaling
FoxO family signaling
Ceramide signaling pathway
Regulation of Androgen receptor activity
p75(NTR)-mediated signaling
ErbB1 downstream signaling
ATF-2 transcription factor network
ErbB2/ErbB3 signaling events
PDGFR-beta signaling pathway
JNK signaling in the CD4+ TCR pathway
Nephrin/Neph1 signaling in the kidney podocyte
Negative effector of Fas and TNF-alpha
Retinoic acid receptors-mediated signaling
Signaling events mediated by Stem cell factor receptor (c-Kit)
EPO signaling pathway
Syndecan-2-mediated signaling events
Ephrin B reverse signaling
p53 pathway
N-cadherin signaling events
S1P2 pathway
Downstream signaling in na&amp
#xef
ve CD8+ T cells
RAC1 signaling pathway
Signaling events mediated by focal adhesion kinase
Glypican 3 network
IL12 signaling mediated by STAT4
PathWhiz Pathway Intracellular Signalling Through Adenosine Receptor A2a and Adenosine
Intracellular Signalling Through Adenosine Receptor A2b and Adenosine
Fc Epsilon Receptor I Signaling in Mast Cells
Reactome NRAGE signals death through JNK
NRIF signals cell death from the nucleus
Oxidative Stress Induced Senescence
FCERI mediated MAPK activation
DSCAM interactions
JNK (c-Jun kinases) phosphorylation and activation mediated by activated human TAK1
Activation of the AP-1 family of transcription factors
Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at DNA double strand breaks
WikiPathways Toll-like receptor signaling pathway
DNA Damage Response (only ATM dependent)
TCR Signaling Pathway
ErbB Signaling Pathway
Insulin Signaling
EGF/EGFR Signaling Pathway
MAPK Signaling Pathway
TGF beta Signaling Pathway
FAS pathway and Stress induction of HSP regulation
Signaling of Hepatocyte Growth Factor Receptor
Kit receptor signaling pathway
Transcriptional activation by NRF2
NLR Proteins
IL-3 Signaling Pathway
Cardiac Hypertrophic Response
Nanoparticle-mediated activation of receptor signaling
Structural Pathway of Interleukin 1 (IL-1)
EBV LMP1 signaling
JAK/STAT
PDGF Pathway
Nanoparticle triggered regulated necrosis
BDNF signaling pathway
Integrated Pancreatic Cancer Pathway
Oncostatin M Signaling Pathway
Corticotropin-releasing hormone
AGE/RAGE pathway
TNF alpha Signaling Pathway
B Cell Receptor Signaling Pathway
Prostate Cancer
TSLP Signaling Pathway
TWEAK Signaling Pathway
Leptin signaling pathway
RANKL/RANK Signaling Pathway
Signalling by NGF
IL-1 signaling pathway
Intrinsic Pathway for Apoptosis
DSCAM interactions
Apoptosis Modulation and Signaling
Type II diabetes mellitus
MicroRNAs in cardiomyocyte hypertrophy
Physiological and Pathological Hypertrophy of the Heart
Regulation of toll-like receptor signaling pathway
Osteoclast Signaling
References
REF 1ClinicalTrials.gov (NCT00033384) CI-1040 in Treating Patients With Advanced Breast, Colon, Pancreatic, or Non-Small Cell Lung Cancer. U.S. National Institutes of Health.
REF 2(http://www.guidetopharmacology.org/) Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 5676).
REF 3ClinicalTrials.gov (NCT01415297) Dose Escalation Study of NKP-1339 to Treat Advanced Solid Tumors. U.S. National Institutes of Health.
REF 4How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6.
REF 5Bioorg Med Chem Lett. 2007 Feb 1;17(3):668-72. Epub 2006 Nov 2.Discovery of a new class of 4-anilinopyrimidines as potent c-Jun N-terminal kinase inhibitors: Synthesis and SAR studies.
REF 6J Med Chem. 2004 Dec 2;47(25):6239-47.Optimization of protein kinase CK2 inhibitors derived from 4,5,6,7-tetrabromobenzimidazole.
REF 7J Med Chem. 2006 Jun 15;49(12):3563-80.Aminopyridine-based c-Jun N-terminal kinase inhibitors with cellular activity and minimal cross-kinase activity.
REF 8Biochem J. 2007 Dec 15;408(3):297-315.The selectivity of protein kinase inhibitors: a further update.
REF 9Biochem J. 2000 Oct 1;351(Pt 1):95-105.Specificity and mechanism of action of some commonly used protein kinase inhibitors.
REF 10Discovery of potent and selective covalent inhibitors of JNK. Chem Biol. 2012 Jan 27;19(1):140-54.
REF 11J Med Chem. 2006 Jul 27;49(15):4455-8.Discovery of potent, highly selective, and orally bioavailable pyridine carboxamide c-Jun NH2-terminal kinase inhibitors.
REF 12(http://www.guidetopharmacology.org/) Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Target id: 1496).

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