| Description |
RWJ 67657 (JNJ 3026582) is an orally active and selective p38α and p38β MAPK inhibitor with IC50s of 1 and 11 μM, respectively. RWJ 67657 displays no activity at p38γ and p38δ, and exhibits cardio protective. Anti-inflammatory and anti-tumor activity[1].
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| Related Catalog |
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| Target |
p38α:1 μM (IC50)
p38β:11 μM (IC50)
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| 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[2]. RWJ67657 (10 μM; 24 hours) decreases colony formation in MCF-7 cells[3]. Cell Proliferation Assay[3] Cell Line: MCF-7 breast carcinoma cells Concentration: 10 μM Incubation Time: 24 hours Result: Did decrease colony formation.
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| 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[2]. 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[4]. Animal Model: db/db mice (male, 8 weeks old) with EPCs[4] Dosage: 50 mg/kg Administration: Administered orally; once per day for 7 consecutive days Result: Increased angiogenesis and neurogenesis of diabetic mice after cotreatment with EPCs transplantation.
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| References |
[1]. Shahin R, et al. Research advances in kinase enzymes and inhibitors for cardiovascular disease treatment. Future Sci OA. 2017 Aug 8;3(4):FSO204. [2]. Wadsworth SA, et al. RWJ 67657, a potent, orally active inhibitor of p38 mitogen-activated protein kinase. J Pharmacol Exp Ther. 1999 Nov;291(2):680-7. [3]. Frigo DE, et al. p38 mitogen-activated protein kinase stimulates estrogen-mediated transcription and proliferation through the phosphorylation and potentiation of the p160 coactivator glucocorticoid receptor-interacting protein 1. Mol Endocrinol. 2006 May;20(5):971-83. [4]. Bai YY, et al. Synergistic Effects of Transplanted Endothelial Progenitor Cells and RWJ 67657 in Diabetic Ischemic Stroke Models. Stroke. 2015 Jul;46(7):1938-46.
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