R-130823

R-130823 is an orally active, highly selective p38α inhibitor with an IC₅₀ of 22 nM against p38α, an IC₅₀ of 820 nM against p38β, and no activity against p38γ or p38δ. R-130823 downregulates downstream cartilage degradation and inflammatory mediators, and inhibits the release of MMP-13, MMP-1 and PGE2. R-130823 reduces hind paw swelling, improves hyperalgesia, and blocks arthritis progression.\nR-130823 is applicable to research related to osteoarthritis and rheumatoid arthritis^[1][2]. In Vitro:R-130823 potently inhibits purified p38α kinase (IC₅₀ = 22 nM), moderately inhibits purified p38β kinase (IC₅₀ = 820 nM), and shows no activity against p38γ or p38δ^[1].
R-130823 (4-2500 nM; 1 h) inhibits the release of MMP-13 (IC₅₀ = 20 nM), MMP-1 (IC₅₀ = 230 nM) and PGE₂ (IC₅₀ = 3.9 nM) induced by IL-1β in human primary chondrocytes^[1].
R-130823 (0.1-10 μM; incubated for 3 weeks with weekly compound supplementation) inhibits IL-1α/oncostatin M-induced collagen cleavage in bovine nasal cartilage explants, with an IC₅₀ of 510 nM^[1]. In Vivo:R-130823 (1-30 mg/kg/day; p.o.; twice daily; 7 days) dose-dependently reduces established hind paw swelling in rat adjuvant-induced arthritis, with a 55% reduction at the highest tested dose of 30 mg/kg/day^[2].
R-130823 (1-30 mg/kg; p.o.; single dose) dose-dependently ameliorates adjuvant-induced hyperalgesia in rats, with sustained analgesic activity lasting up to 24 hours at the highest tested dose of 30 mg/kg^[2].
R-130823 (3-30 mg/kg/day; p.o.; once daily; 14 days) dose-dependently blocks arthritis progression in murine collagen-induced arthritis, with statistically significant suppression of arthritis index (P < 0.0001) and reduced joint tissue inflammation at the highest tested dose of 30 mg/kg/day^[2].