Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTHS0U8)

DTT Name Stress-activated protein kinase JNK2 (JNK2)
Synonyms
Stress-activated protein kinase 1a; SAPK1a; PRKM9; Mitogen-activated protein kinase 9; Mitogen-activated protein kinase 8-interacting protein 2; MAPK 9; MAP kinase 9; Jun-N-terminal kinase 2; JNK-interacting protein 2; JNK-55; JNK MAP kinase scaffold protein 2; JIP-2; Islet-brain-2; IB-2; C-jun-amino-terminal kinase interacting protein 2; C-Jun N-terminal kinase 2
Gene Name MAPK9
DTT Type
Preclinical target
 [1]
Related Disease
Mature T-cell lymphoma [ICD-11: 2A90]
BioChemical Class
Kinase
UniProt ID
MK09_HUMAN
TTD ID
T69375
3D Structure
Download
2D Sequence (FASTA)
Download
3D Structure (PDB)
Download
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
26 Patented Agent(s) Targeting This DTT
Drug Name Drug ID Indication ICD 11 Highest Status REF
7-azaindole derivative 1 DMQL5B7 N. A. N. A. Patented [1]
7-azaindole derivative 2 DMZRM2Q N. A. N. A. Patented [1]
7-azaindole derivative 3 DMQ7BV4 N. A. N. A. Patented [1]
7-azaindole derivative 5 DMV3H98 N. A. N. A. Patented [1]
PMID25991433-Compound-A1 DM89LF0 N. A. N. A. Patented [1]
PMID25991433-Compound-A10 DM39NBT N. A. N. A. Patented [1]
PMID25991433-Compound-A11 DMD59C2 N. A. N. A. Patented [1]
PMID25991433-Compound-A2 DMX7MHC N. A. N. A. Patented [1]
PMID25991433-Compound-A3 DMJ1X53 N. A. N. A. Patented [1]
PMID25991433-Compound-A5 DM5YD1K N. A. N. A. Patented [1]
PMID25991433-Compound-A6 DMFSB9Y N. A. N. A. Patented [1]
PMID25991433-Compound-A7 DM2ISDH N. A. N. A. Patented [1]
PMID25991433-Compound-A8 DMHG4WD N. A. N. A. Patented [1]
PMID25991433-Compound-A9 DMPYCIM N. A. N. A. Patented [1]
PMID25991433-Compound-C1 DM3KWFQ N. A. N. A. Patented [1]
PMID25991433-Compound-D1 DMXSK8Y N. A. N. A. Patented [1]
PMID25991433-Compound-D2 DMLWSNA N. A. N. A. Patented [1]
PMID25991433-Compound-F2 DM37VIQ N. A. N. A. Patented [1]
PMID25991433-Compound-J2 DMZSOCK N. A. N. A. Patented [1]
PMID25991433-Compound-J3 DM17P3F N. A. N. A. Patented [1]
PMID25991433-Compound-J5 DMU75ZX N. A. N. A. Patented [1]
PMID25991433-Compound-O3 DMVOWS5 N. A. N. A. Patented [1]
PMID25991433-Compound-P1 DMD8AX6 N. A. N. A. Patented [1]
PMID25991433-Compound-P4 DMVF1D6 N. A. N. A. Patented [1]
PMID25991433-Compound-P5 DM6FCS9 N. A. N. A. Patented [1]
PMID25991433-Compound-P6 DMNDVC9 N. A. N. A. Patented [1]
------------------------------------------------------------------------------------
⏷ Show the Full List of 26 Patented Agent(s)
1 Preclinical Drug(s) Targeting This DTT
Drug Name Drug ID Indication ICD 11 Highest Status REF
COR-D DMLXMCB T-cell leukaemia 2A90 Preclinical [2]
------------------------------------------------------------------------------------
1 Investigative Drug(s) Targeting This DTT
Drug Name Drug ID Indication ICD 11 Highest Status REF
2,6-Dihydroanthra/1,9-Cd/Pyrazol-6-One DMDN12L Discovery agent N.A. Investigative [3]
------------------------------------------------------------------------------------

References

1 c-Jun N-terminal kinase inhibitors: a patent review (2010 - 2014).Expert Opin Ther Pat. 2015;25(8):849-72.
2 Corchorusin-D directed apoptosis of K562 cells occurs through activation of mitochondrial and death receptor pathways and suppression of AKT/PKB pathway. Cell Physiol Biochem. 2012;30(4):915-26.
3 Pharmacological inhibitors of MAPK pathways. Trends Pharmacol Sci. 2002 Jan;23(1):40-5.