Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TT3IVG2)

DTT Name JNK2 messenger RNA (JNK2 mRNA)
Synonyms
Stress-activated protein kinase 1a (mRNA); SAPK1a (mRNA); PRKM9 (mRNA); Mitogen-activated protein kinase 9 (mRNA); Mitogen-activated protein kinase 8-interacting protein 2 (mRNA); MAPK 9 (mRNA); MAP kinase 9 (mRNA); Jun-N-terminal kinase 2 (mRNA); JNK-interacting protein 2 (mRNA); JNK-55 (mRNA); JNK MAP kinase scaffold protein 2 (mRNA); JIP-2 (mRNA); Islet-brain-2 (mRNA); IB-2 (mRNA); C-jun-amino-terminal kinase interacting protein 2 (mRNA); C-Jun N-terminal kinase 2 (mRNA)
Gene Name MAPK9
DTT Type
Literature-reported target
 [1]
Related Disease
Solid tumour/cancer [ICD-11: 2A00-2F9Z]
BioChemical Class
mRNA target
UniProt ID
MK09_HUMAN
TTD ID
T06037
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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EC Number
EC 2.7.11.24
Sequence
MSDSKCDSQFYSVQVADSTFTVLKRYQQLKPIGSGAQGIVCAAFDTVLGINVAVKKLSRP
FQNQTHAKRAYRELVLLKCVNHKNIISLLNVFTPQKTLEEFQDVYLVMELMDANLCQVIH
MELDHERMSYLLYQMLCGIKHLHSAGIIHRDLKPSNIVVKSDCTLKILDFGLARTACTNF
MMTPYVVTRYYRAPEVILGMGYKENVDIWSVGCIMGELVKGCVIFQGTDHIDQWNKVIEQ
LGTPSAEFMKKLQPTVRNYVENRPKYPGIKFEELFPDWIFPSESERDKIKTSQARDLLSK
MLVIDPDKRISVDEALRHPYITVWYDPAEAEAPPPQIYDAQLEEREHAIEEWKELIYKEV
MDWEERSKNGVVKDQPSDAAVSSNATPSQSSSINDISSMSTEQTLASDTDSSLDASTGPL
EGCR
Function
Extracellular stimuli such as proinflammatory cytokines or physical stress stimulate the stress-activated protein kinase/c-Jun N-terminal kinase (SAP/JNK) signaling pathway. In this cascade, two dual specificity kinases MAP2K4/MKK4 and MAP2K7/MKK7 phosphorylate and activate MAPK9/JNK2. In turn, MAPK9/JNK2 phosphorylates a number of transcription factors, primarily components of AP-1 such as JUN and ATF2 and thus regulates AP-1 transcriptional activity. In response to oxidative or ribotoxic stresses, inhibits rRNA synthesis by phosphorylating and inactivating the RNA polymerase 1-specific transcription initiation factor RRN3. Promotes stressed cell apoptosis by phosphorylating key regulatory factors including TP53 and YAP1. In T-cells, MAPK8 and MAPK9 are required for polarized differentiation of T-helper cells into Th1 cells. Upon T-cell receptor (TCR) stimulation, is activated by CARMA1, BCL10, MAP2K7 and MAP3K7/TAK1 to regulate JUN protein levels. Plays an important role in the osmotic stress-induced epithelial tight-junctions disruption. When activated, promotes beta-catenin/CTNNB1 degradation and inhibits the canonical Wnt signaling pathway. Participates also in neurite growth in spiral ganglion neurons. Phosphorylates the CLOCK-ARNTL/BMAL1 heterodimer and plays a role in the regulation of the circadian clock. Phosphorylates POU5F1, which results in the inhibition of POU5F1's transcriptional activity and enhances its proteosomal degradation. Serine/threonine-protein kinase involved in various processes such as cell proliferation, differentiation, migration, transformation and programmed cell death.
KEGG Pathway
MAPK signaling pathway (hsa04010 )
ErbB signaling pathway (hsa04012 )
Ras signaling pathway (hsa04014 )
cAMP signaling pathway (hsa04024 )
FoxO signaling pathway (hsa04068 )
Sphingolipid signaling pathway (hsa04071 )
Protein processing in endoplasmic reticulum (hsa04141 )
Wnt signaling pathway (hsa04310 )
Osteoclast differentiation (hsa04380 )
Focal adhesion (hsa04510 )
Toll-like receptor signaling pathway (hsa04620 )
NOD-like receptor signaling pathway (hsa04621 )
RIG-I-like receptor signaling pathway (hsa04622 )
T cell receptor signaling pathway (hsa04660 )
Fc epsilon RI signaling pathway (hsa04664 )
TNF signaling pathway (hsa04668 )
Neurotrophin signaling pathway (hsa04722 )
Retrograde endocannabinoid signaling (hsa04723 )
Dopaminergic synapse (hsa04728 )
Inflammatory mediator regulation of TRP channels (hsa04750 )
Insulin signaling pathway (hsa04910 )
GnRH signaling pathway (hsa04912 )
Progesterone-mediated oocyte maturation (hsa04914 )
Prolactin signaling pathway (hsa04917 )
Adipocytokine signaling pathway (hsa04920 )
Type II diabetes mellitus (hsa04930 )
Non-alcoholic fatty liver disease (NAFLD) (hsa04932 )
Epithelial cell signaling in Helicobacter pylori infection (hsa05120 )
Shigellosis (hsa05131 )
Salmonella infection (hsa05132 )
Pertussis (hsa05133 )
Chagas disease (American trypanosomiasis) (hsa05142 )
Toxoplasmosis (hsa05145 )
Tuberculosis (hsa05152 )
Hepatitis C (hsa05160 )
Hepatitis B (hsa05161 )
Influenza A (hsa05164 )
Herpes simplex infection (hsa05168 )
Epstein-Barr virus infection (hsa05169 )
Pathways in cancer (hsa05200 )
Colorectal cancer (hsa05210 )
Pancreatic cancer (hsa05212 )
Choline metabolism in cancer (hsa05231 )
Reactome Pathway
FCERI mediated MAPK activation (R-HSA-2871796 )
JNK (c-Jun kinases) phosphorylation and activation mediated by activated human TAK1 (R-HSA-450321 )
Activation of the AP-1 family of transcription factors (R-HSA-450341 )
Oxidative Stress Induced Senescence (R-HSA-2559580 )

Molecular Interaction Atlas (MIA) of This DTT

Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DTT
9 Investigative Drug(s) Targeting This DTT
Drug Name Drug ID Indication ICD 11 Highest Status REF
AC1LG8KT DMFKV97 Discovery agent N.A. Investigative [1]
Aminopyridine deriv. 2 DM94KQP Discovery agent N.A. Investigative [2]
AS-601245 DMQ95EB Discovery agent N.A. Investigative [3]
IN-1166 DMMS6D3 Discovery agent N.A. Investigative [4]
ISIS 18078 DMHZPJ0 Solid tumour/cancer 2A00-2F9Z Investigative [5]
JNK-IN-8 DMLWYJB Discovery agent N.A. Investigative [6]
N-(4-amino-5-cyano-6-ethoxypyridin-2-yl)acetamide DMY1FMG Discovery agent N.A. Investigative [2]
N-(4-amino-5-cyano-6-phenylpyridin-2-yl)acetamide DMUFVM6 Discovery agent N.A. Investigative [2]
N-(4-amino-6-butoxy-5-cyanopyridin-2-yl)acetamide DMSAD87 Discovery agent N.A. Investigative [2]
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⏷ Show the Full List of 9 Investigative Drug(s)

References

1 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. 2007 Mar 1;17(5):1296-301.
2 Aminopyridine-based c-Jun N-terminal kinase inhibitors with cellular activity and minimal cross-kinase activity. J Med Chem. 2006 Jun 15;49(12):3563-80.
3 The selectivity of protein kinase inhibitors: a further update. Biochem J. 2007 Dec 15;408(3):297-315.
4 Synthesis and biological evaluation of 4(5)-(6-alkylpyridin-2-yl)imidazoles as transforming growth factor-beta type 1 receptor kinase inhibitors. J Med Chem. 2007 Jun 28;50(13):3143-7.
5 US patent application no. 7,425,545, Modulation of C-reactive protein expression.
6 Discovery of potent and selective covalent inhibitors of JNK. Chem Biol. 2012 Jan 27;19(1):140-54.