RWJ-67657

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WARNING: This product is for research use only, not for human or veterinary use.

Description:RWJ-67657 is a potent p38 MAPK inhibitor, which inhibited the release of TNF-alpha by lipopolysaccharide (a monocyte stimulus)-treated human peripheral blood mononuclear cells with an IC(50) of 3 nM, as well as the release of TNF-alpha from peripheral blood mononuclear cells treated with the superantigen staphylococcal enterotoxin B (a T cell stimulus), with an IC(50) value of 13 nM. This compound was approximately 10-fold more potent than the literature standard p38 kinase inhibitor SB 203580 in all p38 dependent in vitro systems tested.

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Chemical Structure

Theoretical Analysis

MedKoo Cat#: 510234Name: RWJ-67657CAS#: 215303-72-3Chemical Formula: C27H24FN3OExact Mass: 425.19034Molecular Weight: 425.49736Elemental Analysis: C, 76.21; H, 5.69; F, 4.46; N, 9.88; O, 3.76

Synonym:RWJ67657; RWJ-67657; RWJ 67657

IUPAC/Chemical Name:4-(4-(4-fluorophenyl)-1-(3-phenylpropyl)-5-(pyridin-4-yl)-1H-imidazol-2-yl)but-3-yn-1-ol

InChi Key:QSUSKMBNZQHHPA-UHFFFAOYSA-N

InChi Code:InChI=1S/C27H24FN3O/c28-24-13-11-22(12-14-24)26-27(23-15-17-29-18-16-23)31(25(30-26)10-4-5-20-32)19-6-9-21-7-2-1-3-8-21/h1-3,7-8,11-18,32H,5-6,9,19-20H2

SMILES Code:OCCC#CC1=NC(C2=CC=C(F)C=C2)=C(C3=CC=NC=C3)N1CCCC4=CC=CC=C4

Technical Data

Additional Information

References

1: Westra J, Kułdo JM, van Rijswijk MH, Molema G,Limburg PC. Chemokine production and E-selectin expression in activatedendothelial cells are inhibited by p38 MAPK (mitogen activated proteinkinase) inhibitor RWJ 67657. Int Immunopharmacol. 2005Jul;5(7-8):1259-69. Epub 2005 Apr 26. PubMed PMID: 15914330.

2: Westra J, Limburg PC, de Boer P, van Rijswijk MH. Effects of RWJ67657, a p38 mitogen activated protein kinase (MAPK) inhibitor, on theproduction of inflammatory mediators by rheumatoid synovial fibroblasts.Ann Rheum Dis. 2004 Nov;63(11):1453-9. PubMed PMID: 15479895; PubMedCentral PMCID: PMC1754789.

3: Westra J, Doornbos-van der Meer B, de Boer P, van Leeuwen MA, vanRijswijk MH, Limburg PC. Strong inhibition of TNF-alpha production andinhibition of IL-8 and COX-2 mRNA expression in monocyte-derivedmacrophages by RWJ 67657, a p38 mitogen-activated protein kinase (MAPK)inhibitor. Arthritis Res Ther. 2004;6(4):R384-92. Epub 2004 Jun 21.PubMed PMID: 15225374; PubMed Central PMCID: PMC464924.

4: Parasrampuria DA, de Boer P, Desai-Krieger D, Chow AT, Jones CR.Single-dose pharmacokinetics and pharmacodynamics of RWJ 67657, aspecific p38 mitogen-activated protein kinase inhibitor: afirst-in-human study. J Clin Pharmacol. 2003 Apr;43(4):406-13. PubMedPMID: 12723461.

5: Faas MM, Moes H, Fijen JW, Muller Kobold AC, Tulleken JE, ZijlstraJG. Monocyte intracellular cytokine production during human endotoxaemiawith or without a second in vitro LPS challenge: effect of RWJ-67657, ap38 MAP-kinase inhibitor, on LPS-hyporesponsiveness. Clin Exp Immunol.2002 Feb;127(2):337-43. PubMed PMID: 11876759; PubMed Central PMCID:PMC1906333.

6: Fijen JW, Zijlstra JG, De Boer P, Spanjersberg R, Tervaert JW, VanDer Werf TS, Ligtenberg JJ, Tulleken JE. Suppression of the clinical andcytokine response to endotoxin by RWJ-67657, a p38 mitogen-activatedprotein-kinase inhibitor, in healthy human volunteers. Clin Exp Immunol.2001 Apr;124(1):16-20. PubMed PMID: 11359438; PubMed Central PMCID:PMC1906020.

7: Wadsworth SA, Cavender DE, Beers SA, Lalan P, Schafer PH, Malloy EA,Wu W, Fahmy B, Olini GC, Davis JE, Pellegrino-Gensey JL, Wachter MP,Siekierka JJ. RWJ 67657, a potent, orally active inhibitor of p38mitogen-activated protein kinase. J Pharmacol Exp Ther. 1999Nov;291(2):680-7. PubMed PMID: 10525088.