WARNING: This product is for research use only, not for human or veterinary use.
MedKoo CAT#: 206022
CAS#: 586379-66-0
Description: PH-797804 is a potent and selectiove inhibitor of p38 mitogen-activated protein (MAP) kinase. PH-797804 reduces tumor growth of the three PDXs, which correlates with impaired colon tumor cell proliferation and survival. The inhibition of p38 MAPK in PDXs results in downregulation of the IL-6/STAT3 signaling pathway, which is a key regulator of colon tumorigenesis. PH-797804 may have therapeutic interest for colon cancer treatment.
MedKoo Cat#: 206022
Name: PH-797804
CAS#: 586379-66-0
Chemical Formula: C22H19BrF2N2O3
Exact Mass: 476.05471
Molecular Weight: 477.29867
Elemental Analysis: C, 55.36; H, 4.01; Br, 16.74; F, 7.96; N, 5.87; O, 10.06
Synonym: PH-797804; PH 797804; PH797804.
IUPAC/Chemical Name: 3-(4-(2,4-difluorobenzyloxy)-3-bromo-6-methyl-2-oxopyridin-1(2H)-yl)-N,4-dimethylbenzamide
InChi Key: KCAJXIDMCNPGHZ-UHFFFAOYSA-N
InChi Code: InChI=1S/C22H19BrF2N2O3/c1-12-4-5-14(21(28)26-3)9-18(12)27-13(2)8-19(20(23)22(27)29)30-11-15-6-7-16(24)10-17(15)25/h4-10H,11H2,1-3H3,(H,26,28)
SMILES Code: O=C(NC)C1=CC=C(C)C(N2C(C)=CC(OCC3=CC=C(F)C=C3F)=C(Br)C2=O)=C1
1: Singh D, Siew L, Christensen J, Plumb J, Clarke GW, Greenaway S, Perros-Huguet C, Clarke N, Kilty I, Tan L. Oral and inhaled p38 MAPK inhibitors: effects on inhaled LPS challenge in healthy subjects. Eur J Clin Pharmacol. 2015 Oct;71(10):1175-84. doi: 10.1007/s00228-015-1920-1. Epub 2015 Aug 13. PubMed PMID: 26265232; PubMed Central PMCID: PMC4564450.
2: Gupta J, Igea A, Papaioannou M, Lopez-Casas PP, Llonch E, Hidalgo M, Gorgoulis VG, Nebreda AR. Pharmacological inhibition of p38 MAPK reduces tumor growth in patient-derived xenografts from colon tumors. Oncotarget. 2015 Apr 20;6(11):8539-51. PubMed PMID: 25890501; PubMed Central PMCID: PMC4496165.
3: Norman P. Investigational p38 inhibitors for the treatment of chronic obstructive pulmonary disease. Expert Opin Investig Drugs. 2015 Mar;24(3):383-92. doi: 10.1517/13543784.2015.1006358. Epub 2015 Jan 20. Review. PubMed PMID: 25599809.
4: Singh D. P38 inhibition in COPD; cautious optimism. Thorax. 2013 Aug;68(8):705-6. doi: 10.1136/thoraxjnl-2013-203498. Epub 2013 Apr 23. PubMed PMID: 23611882.
5: MacNee W, Allan RJ, Jones I, De Salvo MC, Tan LF. Efficacy and safety of the oral p38 inhibitor PH-797804 in chronic obstructive pulmonary disease: a randomised clinical trial. Thorax. 2013 Aug;68(8):738-45. doi: 10.1136/thoraxjnl-2012-202744. Epub 2013 Mar 28. PubMed PMID: 23539534.
6: Xing L, Devadas B, Devraj RV, Selness SR, Shieh H, Walker JK, Mao M, Messing D, Samas B, Yang JZ, Anderson GD, Webb EG, Monahan JB. Discovery and characterization of atropisomer PH-797804, a p38 MAP kinase inhibitor, as a clinical drug candidate. ChemMedChem. 2012 Feb 6;7(2):273-80. doi: 10.1002/cmdc.201100439. Epub 2011 Dec 15. PubMed PMID: 22174080.
7: Selness SR, Devraj RV, Devadas B, Walker JK, Boehm TL, Durley RC, Shieh H, Xing L, Rucker PV, Jerome KD, Benson AG, Marrufo LD, Madsen HM, Hitchcock J, Owen TJ, Christie L, Promo MA, Hickory BS, Alvira E, Naing W, Blevis-Bal R, Messing D, Yang J, Mao MK, Yalamanchili G, Vonder Embse R, Hirsch J, Saabye M, Bonar S, Webb E, Anderson G, Monahan JB. Discovery of PH-797804, a highly selective and potent inhibitor of p38 MAP kinase. Bioorg Med Chem Lett. 2011 Jul 1;21(13):4066-71. doi: 10.1016/j.bmcl.2011.04.121. Epub 2011 May 11. PubMed PMID: 21641211.
8: Hope HR, Anderson GD, Burnette BL, Compton RP, Devraj RV, Hirsch JL, Keith RH, Li X, Mbalaviele G, Messing DM, Saabye MJ, Schindler JF, Selness SR, Stillwell LI, Webb EG, Zhang J, Monahan JB. Anti-inflammatory properties of a novel N-phenyl pyridinone inhibitor of p38 mitogen-activated protein kinase: preclinical-to-clinical translation. J Pharmacol Exp Ther. 2009 Dec;331(3):882-95. doi: 10.1124/jpet.109.158329. Epub 2009 Aug 31. PubMed PMID: 19720877.
9: Xing L, Shieh HS, Selness SR, Devraj RV, Walker JK, Devadas B, Hope HR, Compton RP, Schindler JF, Hirsch JL, Benson AG, Kurumbail RG, Stegeman RA, Williams JM, Broadus RM, Walden Z, Monahan JB. Structural bioinformatics-based prediction of exceptional selectivity of p38 MAP kinase inhibitor PH-797804. Biochemistry. 2009 Jul 14;48(27):6402-11. doi: 10.1021/bi900655f. PubMed PMID: 19496616.
