Therapeutic Targets Database
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TTD Target ID: TTDC00201

Target Information
NameMitogen-activated protein kinase 14    
Type of targetClinical trial target    
SynonymsCRK1    
CSAID binding protein    
CSBP    
Cytokine suppressive anti-inflammatory drug binding protein    
MAP kinase MXI2    
MAP kinase p38    
MAP kinase p38alpha    
MAX-interacting protein 2    
Mitogen-activated protein kinase p38    
Mitogen-activated protein kinase p38 alpha    
P38 Mitogen-activated protein kinase alpha    
P38 mitogen activated protein kinase    
SAPK2A    
DiseaseAdult respiratory distress syndrome
[ICD9: 518.5, 518.82   ICD10: J80]
[1]
Alzheimer's disease
[ICD9: 331.0   ICD10: G30]
[2]
Crescentic glomerulonephritis
[ICD9: 580-582   ICD10: N00, N01, N03, N18]
[3]
Crohn's disease, unspecified
[ICD9: 555   ICD10: K50]
[4]
Cytokine-mediated diseases[5]
Endotoxemia[6]
Inflammation[7][8]
Insulin resistance[9]
Multiple myeloma
[ICD9: 203.0   ICD10: C90.0]
[10]
Psoriasis
[ICD9: 696   ICD10: L40]
[7]
Rheumatoid arthritis, unspecified
[ICD9: 710-719, 714   ICD10: M00-M25, M05-M06]
[11][7]
Skin diseases[12]
Thrombosis
[ICD9: 437.6, 453, 671.5, 671.9   ICD10: I80-I82]
[8]
Drug(s)LosmapimodPhase IICardiovascular disease, COPD and depression[13]
DilmapimodPhase IAcute lung injury & acute respiratory distress syndrome[13]
GSK610677Phase ICOPD[13]
BioChemical ClassTransferases transferring phosphorus-containing groups    
EC NumberEC 2.7.1.37
PathwayAmyotrophic lateral sclerosis (ALS)
Epithelial cell signaling in Helicobacter pylori
Fc epsilon RI signaling pathway
GnRH signaling pathway
Leukocyte transendothelial migration
MAPK signaling pathway
T cell receptor signaling pathway
Toll-like receptor signaling pathway
VEGF signaling pathway
UniProt IDQ16539
PDB Structure1A9U; 1DI9; 1M7Q; 1OZ1; 1W82; 1WBO; 1WBW; 1ZZ2.    
FunctionResponds to activation by environmental stress, pro- inflammatory cytokines and lipopolysaccharide (lps) by phosphorylating a number of transcription factors, such as elk-1 and atf2 and several downstream kinases, such as mapkapk2 and mapkapk5.    
SequenceMSQERPTFYRQELNKTIWEVPERYQNLSPVGSGAYGSVCAAFDTKTGLRVAVKKLSRPFQ SIIHAKRTYRELRLLKHMKHENVIGLLDVFTPARSLEEFNDVYLVTHLMGADLNNIVKCQ KLTDDHVQFLIYQILRGLKYIHSADIIHRDLKPSNLAVNEDCELKILDFGLARHTDDEMT GYVATRWYRAPEIMLNWMHYNQTVDIWSVGCIMAELLTGRTLFPGTDHIDQLKLILRLVG TPGAELLKKISSESARNYIQSLTQMPKMNFANVFIGANPLAVDLLEKMLVLDSDKRITAA QALAHAYFAQYHDPDDEPVADPYDQSFESRDLLIDEWKSLTYDEVISFVPPPLDQEEMES
Related US Patent6,541,477
Target ValidationClick to Find Target Validation Information.    
Inhibitor (5-amino-1-phenyl-1H-pyrazol-4-yl)phenylmethanone[14]
2-Chlorophenol[15]
3- (1-NAPHTHYLMETHOXY)PYRIDIN-2-AMINE[16]
3- (Benzyloxy)Pyridin-2-Amine[15]
4,5,6,7-tetrabromobenzotriazole[17]
4- (2-Ethyl-4-m-tolyl-thiazol-5-yl)-pyridine[18]
4-PHENOXY-N- (PYRIDIN-2-YLMETHYL)BENZAMIDE[16]
4-Phenylsulfanyl-7H-pyrrolo[2,3-d]pyrimidine[19]
4-[ (3,5-diamino-1H-pyrazol-4-yl)diazenyl]phenol[20]
4-[3- (4-FLUOROPHENYL)-1H-PYRAZOL-4-YL]PYRIDINE[16]
6- (4-Fluoro-phenylsulfanyl)-9H-purine[19]
6-Benzylsulfanyl-9H-purine[19]
6-Phenylsulfanyl-9H-purine[19]
6-o-tolylquinazolin-2-amine[21]
9- (4-Fluoro-benzyl)-6-phenylsulfanyl-9H-purine[19]
9-Benzyl-6- (4-fluoro-phenylsulfanyl)-9H-purine[19]
9-Benzyl-6-phenylsulfanyl-9H-purine[19]
B-Octylglucoside[15]
BIRB796[22]
BISINDOLYLMALEIMIDE IX[23]
BMS-640994[24]
CI-1040,   PD-18435,   PD-184352[23]
CNI-1493[4]
CP-808844[25]
Dihydro-quinolinone[26]
Dilmapimod[13]
FR167653[11][3]
GF-109203[23]
GSK610677[13]
GW-788388[27]
Go-6976[23]
IN-1130[28]
IN-1166[28]
Inhibitor of P38 Kinase[15]
KN-62[23]
KT-5720[23]
L-779450[29]
LY-294002[23]
Losmapimod[13]
ML-3163[30]
ML-3375[31]
ML-3403[31]
N- (3-[32]
N- (3-[32]
N- (4-[32]
N- (4-fluorobenzyl)-N-[33]
N- (4-methyl-benzyl)-4-phenoxy-benzamide[32]
PAMAPIMOD[34]
PD-0166326,   PD-166326[35]
PD-0173956[35]
PD-98059[23]
Phenyl- (3-phenyl-1H-indazol-6-yl)-amine[36]
Pyridinyl imidazole compounds[7]
RO-316233[23]
RWJ-68354[37]
Ro-3201195[38]
SB 202190[6]
SB 203580[8][39]
SB 235699[7]
SB-202190[23]
SB-203580[26]
SB-216995[26]
SB-218655[26]
SB-220025[26]
SB-227931[40]
SB-242235[41]
SB220025[15]
SCIO469[7]
SK&F-86002,   SK-86002[30]
STAUROSPORINONE[23]
TYRPHOSTIN AG-1478[42]
Triazolopyridine[16]
U-0126[23]
VK-19911[43]
Vertex 745 (VX745)[7]
ZM-336372[44]
talmapimod[34]
Cross References 3D Structure
Related Literature
On-Line Medical Dictionary
Ref 1p38 mitogen-activated protein kinase inhibition attenuates intercellular adhesion molecule-1 up-regulation on human pulmonary microvascular endothelial cells. Surgery. 1998 Aug;124(2):403-7; discussion 408. To Reference
Ref 2p38 mitogen activated protein kinase as a therapeutic target for Alzheimer's disease. J Mol Neurosci. 2002 Dec;19(3):295-9. To Reference
Ref 3Involvement of p38 mitogen-activated protein kinase followed by chemokine expression in crescentic glomerulonephritis. Am J Kidney Dis. 2001 Dec;38(6):1169-77. To Reference
Ref 4From extracellular to intracellular targets, inhibiting MAP kinases in treatment of Crohn's disease. Ann N Y Acad Sci. 2002 Nov;973:349-58. To Reference
Ref 5Inhibitors of p38 MAP kinase: therapeutic intervention in cytokine-mediated diseases. Curr Med Chem. 1999 Sep;6(9):807-23. To Reference
Ref 6Inhibition of p38 MAPK decreases myocardial TNF-alpha expression and improves myocardial function and survival in endotoxemia. Cardiovasc Res. 2003 Oct 1;59(4):893-900. To Reference
Ref 7Pharmacological inhibitors of MAPK pathways. Trends Pharmacol Sci. 2002 Jan;23(1):40-5. To Reference
Ref 8The p38 mitogen-activated protein kinase pathway plays a critical role in thrombin-induced endothelial chemokine production and leukocyte recruitment. Blood. 2001 Aug 1;98(3):667-73. To Reference
Ref 9Gliclazide increases insulin receptor tyrosine phosphorylation but not p38 phosphorylation in insulin-resistant skeletal muscle cells. J Exp Biol. 2002 Dec;205(Pt 23):3739-46. To Reference
Ref 10Blood. 2003 Jan 15;101(2):703-5. Epub 2002 Sep 5.Targeting p38 MAPK inhibits multiple myeloma cell growth in the bone marrow milieu. To Reference
Ref 11Prevention of the onset and progression of collagen-induced arthritis in rats by the potent p38 mitogen-activated protein kinase inhibitor FR167653. Arthritis Rheum. 2003 Sep;48(9):2670-81. To Reference
Ref 12High efficiency of 5-aminolevulinate-photodynamic treatment using UVA irradiation. Carcinogenesis. 2001 Jun;22(6):879-83. To Reference
Ref 13GSK. Product Development Pipeline. February 2009. To Reference
Ref 14J Med Chem. 2006 Mar 9;49(5):1562-75.Discovery of S-[5-amino-1-(4-fluorophenyl)-1H-pyrazol-4-yl]-[3-(2,3-dihydroxypropoxy)phenyl]methanone (RO3201195), an orally bioavailable and highly selective inhibitor of p38 MAP kinase. To Reference
Ref 15Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. To Reference
Ref 16Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE: The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42. To Reference
Ref 17J Med Chem. 2004 Dec 2;47(25):6239-47.Optimization of protein kinase CK2 inhibitors derived from 4,5,6,7-tetrabromobenzimidazole. To Reference
Ref 18J Med Chem. 2005 Sep 22;48(19):5966-79.Novel inhibitor of p38 MAP kinase as an anti-TNF-alpha drug: discovery of N-[4-[2-ethyl-4-(3-methylphenyl)-1,3-thiazol-5-yl]-2-pyridyl]benzamide (TAK-715) as a potent and orally active anti-rheumatoid arthritis agent. To Reference
Ref 19J Med Chem. 2005 Feb 10;48(3):710-22.Synthesis and biological testing of purine derivatives as potential ATP-competitive kinase inhibitors. To Reference
Ref 20J Med Chem. 2006 Nov 2;49(22):6500-9.4-arylazo-3,5-diamino-1H-pyrazole CDK inhibitors: SAR study, crystal structure in complex with CDK2, selectivity, and cellular effects. To Reference
Ref 21J Med Chem. 2006 Sep 21;49(19):5671-86.Discovery of aminoquinazolines as potent, orally bioavailable inhibitors of Lck: synthesis, SAR, and in vivo anti-inflammatory activity. To Reference
Ref 22Bioorg Med Chem. 2010 Aug 1;18(15):5738-48. Epub 2010 Jun 4.The design, synthesis, and evaluation of 8 hybrid DFG-out allosteric kinase inhibitors: a structural analysis of the binding interactions of Gleevec, Nexavar, and BIRB-796. To Reference
Ref 23Biochem J. 2000 Oct 1;351(Pt 1):95-105.Specificity and mechanism of action of some commonly used protein kinase inhibitors. To Reference
Ref 24Bioorg Med Chem Lett. 2008 Mar 15;18(6):1762-7. Epub 2008 Feb 16.The discovery of (R)-2-(sec-butylamino)-N-(2-methyl-5-(methylcarbamoyl)phenyl) thiazole-5-carboxamide (BMS-640994)-A potent and efficacious p38alpha MAP kinase inhibitor. To Reference
Ref 25Bioorg Med Chem Lett. 2006 Aug 15;16(16):4339-44. Epub 2006 Jun 12.Structure-activity relationships of triazolopyridine oxazole p38 inhibitors: identification of candidates for clinical development. To Reference
Ref 26Bioorg Med Chem. 2010 Mar 15;18(6):2204-18. Epub 2010 Feb 8.In silico search for multi-target anti-inflammatories in Chinese herbs and formulas. To Reference
Ref 27J Med Chem. 2006 Apr 6;49(7):2210-21.Discovery of 4-{4-[3-(pyridin-2-yl)-1H-pyrazol-4-yl]pyridin-2-yl}-N-(tetrahydro-2H- pyran-4-yl)benzamide (GW788388): a potent, selective, and orally active transforming growth factor-beta type I receptor inhibitor. To Reference
Ref 28Bioorg Med Chem Lett. 2008 Jul 15;18(14):4006-10. Epub 2008 Jun 6.Synthesis and biological evaluation of trisubstituted imidazole derivatives as inhibitors of p38alpha mitogen-activated protein kinase. To Reference
Ref 29Bioorg Med Chem Lett. 2006 Jan 15;16(2):378-81. Epub 2005 Nov 2.The identification of potent and selective imidazole-based inhibitors of B-Raf kinase. To Reference
Ref 30J Med Chem. 2002 Jun 20;45(13):2733-40.From imidazoles to pyrimidines: new inhibitors of cytokine release. To Reference
Ref 31J Med Chem. 2003 Jul 17;46(15):3230-44.Novel substituted pyridinyl imidazoles as potent anticytokine agents with low activity against hepatic cytochrome P450 enzymes. To Reference
Ref 32Bioorg Med Chem Lett. 2005 Dec 1;15(23):5274-9. Epub 2005 Sep 19.Two classes of p38alpha MAP kinase inhibitors having a common diphenylether core but exhibiting divergent binding modes. To Reference
Ref 33Bioorg Med Chem Lett. 2010 Apr 15;20(8):2560-3. Epub 2010 Mar 2.Amide-based inhibitors of p38alpha MAP kinase. Part 2: design, synthesis and SAR of potent N-pyrimidyl amides. To Reference
Ref 34J Med Chem. 2010 Mar 25;53(6):2345-53.Selective p38alpha inhibitors clinically evaluated for the treatment of chronic inflammatory disorders. To Reference
Ref 35Bioorg Med Chem Lett. 2009 Dec 15;19(24):6872-6. Epub 2009 Oct 23.Structure-activity relationships of 6-(2,6-dichlorophenyl)-8-methyl-2-(phenylamino)pyrido[2,3-d]pyrimidin-7-ones: toward selective Abl inhibitors. To Reference
Ref 36Bioorg Med Chem Lett. 2005 Nov 15;15(22):5095-9.Design and synthesis of 6-anilinoindazoles as selective inhibitors of c-Jun N-terminal kinase-3. To Reference
Ref 37Bioorg Med Chem Lett. 2003 Feb 10;13(3):347-50.Imidazopyrimidines, potent inhibitors of p38 MAP kinase. To Reference
Ref 38Bioorg Med Chem Lett. 2008 Jul 1;18(13):3745-8. Epub 2008 May 16.Microwave-assisted synthesis of 5-aminopyrazol-4-yl ketones and the p38(MAPK) inhibitor RO3201195 for study in Werner syndrome cells. To Reference
Ref 39Mini Rev Med Chem. 2007 Nov;7(11):1108-19.Privileged structures: a useful concept for the rational design of new lead drug candidates. To Reference
Ref 40Bioorg Med Chem Lett. 2005 Nov 1;15(21):4666-70.The neuroprotective action of JNK3 inhibitors based on the 6,7-dihydro-5H-pyrrolo[1,2-a]imidazole scaffold. To Reference
Ref 41Bioorg Med Chem Lett. 2008 Aug 1;18(15):4433-7. Epub 2008 Jun 12.Biphenyl amide p38 kinase inhibitors 4: DFG-in and DFG-out binding modes. To Reference
Ref 42Bioorg Med Chem Lett. 2004 Nov 1;14(21):5389-94.Novel, potent and selective anilinoquinazoline and anilinopyrimidine inhibitors of p38 MAP kinase. To Reference
Ref 43J Med Chem. 2003 Dec 18;46(26):5651-62.Synthesis and structure-activity relationship of aminobenzophenones. A novel class of p38 MAP kinase inhibitors with high antiinflammatory activity. To Reference
Ref 44Bioorg Med Chem Lett. 2004 Nov 1;14(21):5383-7.A novel series of p38 MAP kinase inhibitors for the potential treatment of rheumatoid arthritis. To Reference



 

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Professor in Department of Pharmacy
National University of Singapore, Singapore


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