GDC-0834

GDC-0834 is a potent and selective BTK inhibitor. GDC-0834 inhibits BTK with an in vitro IC₅₀ of 5.9 and 6.4 nM in biochemical and cellular assays, respectively, and in vivo IC₅₀ of 1.1 and 5.6 μM in mouse and rat, respectively. IC50 & Target: IC50: 5.9 nM (BTK)^[1] In Vitro: GDC-0834 suppresses BTK kinase activity with an IC₅₀ value of 5.9±1.1 nM with Hill slope value of ?0.84±0.07 (mean±S.E.)^[1]. GDC-0834 is shown to be a potent reversible inhibitor of six known aldehyde oxidase (AO) substrates with IC₅₀ values ranging from 0.86 to 1.87 μM^[2]. In Vivo: The treatment of BALB/c mice with GDC-0834 results in dose-dependent inhibition of pBTK-Tyr223. Animals dosed with 150 or 100 mg/kg GDC-0834 for 2 h show complete inhibition of pBTK-Tyr223 levels in blood, with a mean inhibition of 97 and 96%, respectively. In the rat CIA study, GDC-0834 inhibits pBTK-Tyr223 in rat blood in a dose-dependent manner. The IC₅₀ estimate of pBTK-Tyr223 inhibition in rats is determined to be 5.6±1.6 μM with m of 0.51±0.087 (mean±S.E.)^[1].