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LY2090314

CAS No. : 603288-22-8

MCE 国际站：LY2090314

产品活性：LY2090314 是一种有效的 GSK-3 抑制剂，抑制 GSK-3α 和 GSK-3β，IC₅₀ 值分别为 1.5 nM 和 0.9 nM。

研究领域：PI3K/Akt/mTOR  |  Stem Cell/Wnt

作用靶点：GSK-3

In Vitro: LY2090314 (20 nM) promotes a time-dependent stabilization of β-catenin total protein as well as an induction of Axin2. LY2090314 is highly selective towards GSK3 as demonstrated by its fold selectivity relative to a large panel of kinases. LY2090314 potently induces apoptotic cell death in a panel of melanoma cell lines irrespective of BRAF mutation status. Cell death induced by LY2090314 is dependent on β-catenin and GSK3β knockdown increases the sensitivity of cells to LY2090314. LY2090314 remains active in cell lines resistant to PLX4032 and has an independent mechanism of action.

In Vivo: LY2090314 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 is rapidly cleared by extensive metabolism with negligible circulating metabolite exposures due to biliary excretion of metabolites into feces with no apparent intestinal reabsorption.
LY2090314 (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.

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