Org 48762-0

Org 48762-0 (UR13870) is a potent, orally active and selective p38 inhibitor with an EC₅₀ of 0.1 μM for p38α kinase. Org 48762-0 shows a high degree of kinase selectivity for p38α and p38β over other kinases. Org 48762-0 reduces Lipopolysaccharides (HY-D1056) (LPS)-induced TNFα release. Org 48762-0 can be used for the study of rheumatoid arthritis (RA) and Werner syndrome^[1][2]. In Vitro:Org 48762-0 completely inhibits LPS-induced TNFα release from peripheral blood mononuclear cells (PBMC) with an EC₅₀ value of 0.06 μM. Org 48762-0 dose-dependently inhibits stress-induced MK2 translocation, with an EC₅₀ value of 0.69 μM^[1].
Org 48762-0 (0.1-10 μM; pre-incubated for 30 min) is capable of inhibiting IL-1β-induced signalling cascades, consequently interfering with production of proinflammatory cytokines^[1].
In Vivo:Org 48762-0 (0.3-3 mg/kg; p.o; once) inhibits LPS-induced cytokine production in mice^[1].
In mice, Org 48762-0 shows an oral bioavailability of 85% and exhibits sustained systemic exposure (>1 μM) for 24 h after a dose of 4.0 mg/kg. When Org 48762-0 is administered intravenously (1.6 mg/kg), the compound shows a low volume of distribution in steady state (Vss: 50.0 mL/kg) and a low clearance (CL: 9.0 mL/h/kg), resulting in a mean residence time of 5.3 h^[1].