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 effect. Anti-inflammatory and anti-tumor activity^[1]. 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]. 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].