Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TT056SO)

• DTT Name: Stress-activated protein kinase JNK3 (JNK3)
• Synonyms: Stress-activated protein kinase 1b; SAPK1b; PRKM10; Mitogen-activated protein kinase 10; MAPK 10; MAP kinase p49 3F12; MAP kinase 10; JNK3A; C-Jun N-terminal kinase 3
• Gene Name: MAPK10
• DTT Type: Patented-recorded target; [1]
• BioChemical Class: Kinase
• UniProt ID: MK10_HUMAN
• TTD ID: T00663
• EC Number: EC 2.7.11.24
• Sequence:
  MSLHFLYYCSEPTLDVKIAFCQGFDKQVDVSYIAKHYNMSKSKVDNQFYSVEVGDSTFTV
  LKRYQNLKPIGSGAQGIVCAAYDAVLDRNVAIKKLSRPFQNQTHAKRAYRELVLMKCVNH
  KNIISLLNVFTPQKTLEEFQDVYLVMELMDANLCQVIQMELDHERMSYLLYQMLCGIKHL
  HSAGIIHRDLKPSNIVVKSDCTLKILDFGLARTAGTSFMMTPYVVTRYYRAPEVILGMGY
  KENVDIWSVGCIMGEMVRHKILFPGRDYIDQWNKVIEQLGTPCPEFMKKLQPTVRNYVEN
  RPKYAGLTFPKLFPDSLFPADSEHNKLKASQARDLLSKMLVIDPAKRISVDDALQHPYIN
  VWYDPAEVEAPPPQIYDKQLDEREHTIEEWKELIYKEVMNSEEKTKNGVVKGQPSPSGAA
  VNSSESLPPSSSVNDISSMSTDQTLASDTDSSLEASAGPLGCCR
• 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 MAPK10/JNK3. In turn, MAPK10/JNK3 phosphorylates a number of transcription factors, primarily components of AP-1 such as JUN and ATF2 and thus regulates AP-1 transcriptional activity. Plays regulatory roles in the signaling pathways during neuronal apoptosis. Phosphorylates the neuronal microtubule regulator STMN2. Acts in the regulation of the amyloid-beta precursor protein/APP signaling during neuronal differentiation by phosphorylating APP. Participates also in neurite growth in spiral ganglion neurons. Phosphorylates the CLOCK-ARNTL/BMAL1 heterodimer and plays a role in the photic regulation of the circadian clock. Serine/threonine-protein kinase involved in various processes such as neuronal proliferation, differentiation, migration 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)
  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

17 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 4	DMW3EMH	N. A.	N. A.	Patented	[1]
7-azaindole derivative 5	DMV3H98	N. A.	N. A.	Patented	[1]
7-azaindole derivative 6	DM8X5GP	N. A.	N. A.	Patented	[1]
7-azaindole derivative 7	DMB1WQZ	N. A.	N. A.	Patented	[1]
PMID25991433-Compound-A1	DM89LF0	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]

12 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	[2]
9-(4-Hydroxyphenyl)-2,7-Phenanthroline	DMOL01E	Discovery agent	N.A.	Investigative	[2]
AC1LG8KT	DMFKV97	Discovery agent	N.A.	Investigative	[3]
Aminopyridine deriv. 2	DM94KQP	Discovery agent	N.A.	Investigative	[4]
AMP-PNP	DMTOK1D	Discovery agent	N.A.	Investigative	[5]
AS-601245	DMQ95EB	Discovery agent	N.A.	Investigative	[6]
ELN-864709	DM2DERW	Central nervous system injury	KA40	Investigative	[3]
JNK-IN-8	DMLWYJB	Discovery agent	N.A.	Investigative	[7]
N-(4-amino-5-cyano-6-ethoxypyridin-2-yl)acetamide	DMY1FMG	Discovery agent	N.A.	Investigative	[4]
N-(4-amino-5-cyano-6-phenylpyridin-2-yl)acetamide	DMUFVM6	Discovery agent	N.A.	Investigative	[4]
NSC-656158	DM52NOI	Discovery agent	N.A.	Investigative	[8]
Phenyl-(3-phenyl-1H-indazol-6-yl)-amine	DMDCTNU	Discovery agent	N.A.	Investigative	[9]

References

• [1] c-Jun N-terminal kinase inhibitors: a patent review (2010 - 2014).Expert Opin Ther Pat. 2015;25(8):849-72.
• [2] How many drug targets are there Nat Rev Drug Discov. 2006 Dec;5(12):993-6.
• [3] URL: 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: 1498).
• [4] 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.
• [5] The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42.
• [6] A systematic interaction map of validated kinase inhibitors with Ser/Thr kinases. Proc Natl Acad Sci U S A. 2007 Dec 18;104(51):20523-8.
• [7] Discovery of potent and selective covalent inhibitors of JNK. Chem Biol. 2012 Jan 27;19(1):140-54.
• [8] Synthesis and preclinical evaluations of 2-(2-fluorophenyl)-6,7-methylenedioxyquinolin-4-one monosodium phosphate (CHM-1-P-Na) as a potent antitumo... J Med Chem. 2010 Feb 25;53(4):1616-26.
• [9] Design and synthesis of 6-anilinoindazoles as selective inhibitors of c-Jun N-terminal kinase-3. Bioorg Med Chem Lett. 2005 Nov 15;15(22):5095-9.