LY2090314 (GMP)

LY2090314 (GMP) is LY2090314 (HY-16294) produced by using GMP guidelines. GMP small molecules works appropriately as an auxiliary reagent for cell therapy manufacture. LY2090314 is a potent inhibitor of glycogen synthase kinase-3 (GSK-3) with IC₅₀ values of 1.5 nM and 0.9 nM for GSK-3α and GSK-3β, respectively. In Vitro:LY2090314 (GMP) (20 nM) promotes a time-dependent stabilization of β-catenin total protein as well as an induction of Axin2. LY2090314 (GMP) is highly selective towards GSK3 as demonstrated by its fold selectivity relative to a large panel of kinases. LY2090314 (GMP) potently induces apoptotic cell death in a panel of melanoma cell lines irrespective of BRAF mutation status. Cell death induced by (GMP) is dependent on β-catenin and GSK3β knockdown increases the sensitivity of cells to (GMP). (GMP) remains active in cell lines resistant to PLX4032 and has an independent mechanism of action^[2]. In Vivo:LY2090314 (GMP) exhibits high clearance (approximating hepatic blood flow) and a moderate volume of distribution (appr 1-2 L/kg) resulting in rapid elimination (half-life appr 0.4, 0.7, and 1.8-3.4 hours in rats, dogs, and humans, respectively). LY2090314 (GMP) is rapidly cleared by extensive metabolism with negligible circulating metabolite exposures due to biliary excretion of metabolites into feces with no apparent intestinal reabsorption^[1].
LY2090314 (GMP) (25 mg/kg Q3D, i.v.) elevates Axin2 gene expression in vivo, demonstrates single agent activity in the A375 xenograft model of melanoma and enhances the efficacy of DTIC^[2].