RWJ 67657

Names

[ Name ]:
RWJ 67657

[Synonym ]:
4-(4-(4-Fluorophenyl)-1-(3-phenylpropyl)-5-(4-pyridinyl)-1H-imidazol-2-yl)-3-butyn-1-ol
4-[4-(4-Fluorophenyl)-1-(3-phenylpropyl)-5-(pyridin-4-yl)-1H-imidazol-2-yl]but-3-yn-1-ol
3-Butyn-1-ol, 4-(4-(4-fluorophenyl)-1-(3-phenylpropyl)-5-(4-pyridinyl)-1H-imidazol-2-yl)-
3-Butyn-1-ol, 4-[4-(4-fluorophenyl)-1-(3-phenylpropyl)-5-(4-pyridinyl)-1H-imidazol-2-yl]-
4-[4-(4-Fluorophenyl)-1-(3-phenylpropyl)-5-(4-pyridinyl)-1H-imidazol-2-yl]-3-butyn-1-ol
4-(4-Fluorophenyl)-2-(4-hydroxy-1-butynyl)-1-(3-Phenylpropyl)-5-(4-Pyridyl)imidazole
RWJ-67657

Biological Activity

[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].

[Related Catalog]:

Research Areas >> Cancer

Research Areas >> Cardiovascular Disease

Signaling Pathways >> MAPK/ERK Pathway >> p38 MAPK

Research Areas >> Inflammation/Immunology

[Target]

p38α:1 μM (IC50)

p38β:11 μM (IC50)

[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.

[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.

[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.