RWJ 67657

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.

Product information

CAS Number: 215303-72-3

Molecular Weight: 425.50

Formula: C27H24FN3O

Synonym:

RWJ67657

RWJ-67657

RWJ 67657

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

Smiles: OCCC#CC1=NC(C2=CC=C(F)C=C2)=C(C2C=CN=CC=2)N1CCCC1C=CC=CC=1

InChiKey: QSUSKMBNZQHHPA-UHFFFAOYSA-N

InChi: 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

Technical Data

Appearance: Solid Power.

Purity: ≥98% (or refer to the Certificate of Analysis)

Solubility: Soluble in DMSO, not in water

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical or refer to Certificate of Analysis

Storage Condition: Dry, dark and -20 ^oC for 1 year or refer to the Certificate of Analysis.

Shelf Life: ≥12 months if stored properly.

Stock Solution Storage: 0 - 4 ^oC for 1 month or refer to the Certificate of Analysis.

Drug Formulation: To be determined.

HS Tariff Code: 382200

How to use

In Vitro:

RWJ 67657 inhibits the release of TNF-α by lipopolysaccharide (LPS)-treated human peripheral blood mononuclear cells with an IC50 of 3 nM, as well as the release of TNF-α from peripheral blood mononuclear cells treated with the superantigen staphylococcal enterotoxin B, with an IC50 value of 13 nM.RWJ 67657 (10 μM; 24 hours) decreases colony formation in MCF-7 cells.

In Vivo:

RWJ 67657 inhibits TNF-alpha production in lipopolysaccharide-injected mice (87% inhibition at 50 mg/kg) and in rats (91% inhibition at 25 mg/kg) after oral administration.RWJ 67657 (50 mg/kg; administered orally; once per day for 7 consecutive days) displays a potent anti-inflammatory effect. By both improving the functioning of endothelial progenitor cells (EPCs) and reducing inflammation, EPC transplantation plus RWJ 67657 administration synergistically promotes angiogenesis and neurogenesis after diabetic stroke.

References:

1. Westra J, Kułdo JM, van Rijswijk MH, Molema G, Limburg PC. Chemokine production and E-selectin expression in activated endothelial cells are inhibited by p38 MAPK (mitogen activated protein kinase) inhibitor RWJ 67657. Int Immunopharmacol. 2005 Jul;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 RWJ 67657, a p38 mitogen activated protein kinase (MAPK) inhibitor, on the production of inflammatory mediators by rheumatoid synovial fibroblasts. Ann Rheum Dis. 2004 Nov;63(11):1453-9. PubMed PMID: 15479895; PubMed Central PMCID: PMC1754789.
3. Parasrampuria DA, de Boer P, Desai-Krieger D, Chow AT, Jones CR. Single-dose pharmacokinetics and pharmacodynamics of RWJ 67657, a specific p38 mitogen-activated protein kinase inhibitor: a first-in-human study. J Clin Pharmacol. 2003 Apr;43(4):406-13. PubMed PMID: 12723461.
4. Faas MM, Moes H, Fijen JW, Muller Kobold AC, Tulleken JE, Zijlstra JG. Monocyte intracellular cytokine production during human endotoxaemia with or without a second in vitro LPS challenge: effect of RWJ-67657, a p38 MAP-kinase inhibitor, on LPS-hyporesponsiveness. Clin Exp Immunol. 2002 Feb;127(2):337-43. PubMed PMID: 11876759; PubMed Central PMCID: PMC1906333.
5. Fijen JW, Zijlstra JG, De Boer P, Spanjersberg R, Tervaert JW, Van Der Werf TS, Ligtenberg JJ, Tulleken JE. Suppression of the clinical and cytokine response to endotoxin by RWJ-67657, a p38 mitogen-activated protein-kinase inhibitor, in healthy human volunteers. Clin Exp Immunol. 2001 Apr;124(1):16-20. PubMed PMID: 11359438; PubMed Central PMCID: PMC1906020.
6. 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 p38 mitogen-activated protein kinase. J Pharmacol Exp Ther. 1999 Nov;291(2):680-7. PubMed PMID: 10525088.

Products are for research use only. Not for human use.