WARNING: This product is for research use only, not for human or veterinary use.
MedKoo CAT#: 510233
Description: Pamapimod is a novel p38 mitogen-activated protein kinase inhibitor. Pamapimod inhibited p38alpha and p38beta enzymatic activity, with IC(50) values of 0.014 +/- 0.002 and 0.48 +/- 0.04 microM, respectively. There was no activity against p38delta or p38gamma isoforms. When profiled across 350 kinases, pamapimod bound only to four kinases in addition to p38. Cellular potency was assessed using phosphorylation of heat shock protein-27 and c-Jun as selective readouts for p38 and c-Jun NH(2)-terminal kinase (JNK), respectively. Pamapimod inhibited p38 (IC(50), 0.06 microM), but inhibition of JNK was not detected. Pamapimod also inhibited lipopolysaccharide (LPS)-stimulated tumor necrosis factor (TNF) alpha production by monocytes, interleukin (IL)-1beta production in human whole blood, and spontaneous TNFalpha production by synovial explants from RA patients. Pamapimod is a potent, selective inhibitor of p38alpha with the ability to inhibit the signs and symptoms of RA and other autoimmune diseases. (copied from J Pharmacol Exp Ther. 2008 Dec;327(3):610-9.)
MedKoo Cat#: 510233
Chemical Formula: C19H20F2N4O4
Exact Mass: 406.14526
Molecular Weight: 406.38
Elemental Analysis: C, 56.15; H, 4.96; F, 9.35; N, 13.79; O, 15.75
Synonym: Pamapimod; R 1503; R1503; R-1503; Ro 4402257; Ro4402257; Ro-4402257.
IUPAC/Chemical Name: 6-(2,4-Difluorophenoxy)-2-[[3-hydroxy-1-(2-hydroxyethyl)propyl]amino]-8-methylpyrido[2,3-d]pyrimidin-7(8H)-one
InChi Key: JYYLVUFNAHSSFE-UHFFFAOYSA-N
InChi Code: InChI=1S/C19H20F2N4O4/c1-25-17-11(10-22-19(24-17)23-13(4-6-26)5-7-27)8-16(18(25)28)29-15-3-2-12(20)9-14(15)21/h2-3,8-10,13,26-27H,4-7H2,1H3,(H,22,23,24)
SMILES Code: O=C1C(OC2=CC=C(F)C=C2F)=CC3=CN=C(NC(CCO)CCO)N=C3N1C
1: Zhang X, Fettner S, Winter E, Masjedizadeh M, Hisoire G. Metabolism and excretion of a novel p38 MAP kinase inhibitor pamapimod in healthy male subjects. Int J Clin Pharmacol Ther. 2011 Jun;49(6):345-52. PubMed PMID: 21612741.
2: Goldstein DM, Soth M, Gabriel T, Dewdney N, Kuglstatter A, Arzeno H, Chen J, Bingenheimer W, Dalrymple SA, Dunn J, Farrell R, Frauchiger S, La Fargue J, Ghate M, Graves B, Hill RJ, Li F, Litman R, Loe B, McIntosh J, McWeeney D, Papp E, Park J, Reese HF, Roberts RT, Rotstein D, San Pablo B, Sarma K, Stahl M, Sung ML, Suttman RT, Sjogren EB, Tan Y, Trejo A, Welch M, Weller P, Wong BR, Zecic H. Discovery of 6-(2,4-difluorophenoxy)-2-[3-hydroxy-1-(2-hydroxyethyl)propylamino]-8-methyl-8H-p yrido[2,3-d]pyrimidin-7-one (pamapimod) and 6-(2,4-difluorophenoxy)-8-methyl-2-(tetrahydro-2H-pyran-4-ylamino)pyrido[2,3-d]py rimidin-7(8H)-one (R1487) as orally bioavailable and highly selective inhibitors of p38α mitogen-activated protein kinase. J Med Chem. 2011 Apr 14;54(7):2255-65. doi: 10.1021/jm101423y. Epub 2011 Mar 4. PubMed PMID: 21375264.
3: Doggrell SA, Christensen AM. Does the p38 MAP kinase inhibitor pamapimod have potential for the treatment of rheumatoid arthritis? Expert Opin Pharmacother. 2010 Oct;11(14):2437-42. doi: 10.1517/14656566.2010.507631. PubMed PMID: 20666701.
4: Zhang X, Huang Y, Navarro MT, Hisoire G, Caulfield JP. A proof-of-concept and drug-drug interaction study of pamapimod, a novel p38 MAP kinase inhibitor, with methotrexate in patients with rheumatoid arthritis. J Clin Pharmacol. 2010 Sep;50(9):1031-8. doi: 10.1177/0091270009357433. Epub 2010 Jan 25. PubMed PMID: 20100913.
5: Alten RE, Zerbini C, Jeka S, Irazoque F, Khatib F, Emery P, Bertasso A, Rabbia M, Caulfield JP. Efficacy and safety of pamapimod in patients with active rheumatoid arthritis receiving stable methotrexate therapy. Ann Rheum Dis. 2010 Feb;69(2):364-7. doi: 10.1136/ard.2008.104802. Epub 2009 Apr 8. Erratum in: Ann Rheum Dis. 2011 Aug;70(8):1519. PubMed PMID: 19357113.
6: Cohen SB, Cheng TT, Chindalore V, Damjanov N, Burgos-Vargas R, Delora P, Zimany K, Travers H, Caulfield JP. Evaluation of the efficacy and safety of pamapimod, a p38 MAP kinase inhibitor, in a double-blind, methotrexate-controlled study of patients with active rheumatoid arthritis. Arthritis Rheum. 2009 Feb;60(2):335-44. doi: 10.1002/art.24266. PubMed PMID: 19180516.
7: Hill RJ, Dabbagh K, Phippard D, Li C, Suttmann RT, Welch M, Papp E, Song KW, Chang KC, Leaffer D, Kim YN, Roberts RT, Zabka TS, Aud D, Dal Porto J, Manning AM, Peng SL, Goldstein DM, Wong BR. Pamapimod, a novel p38 mitogen-activated protein kinase inhibitor: preclinical analysis of efficacy and selectivity. J Pharmacol Exp Ther. 2008 Dec;327(3):610-9. doi: 10.1124/jpet.108.139006. Epub 2008 Sep 5. PubMed PMID: 18776065.