GSK2945 (hydrochloride)

457.80

H2O : < 0.1 mg/mL (insoluble); DMSO : 20.83 mg/mL (45.50 mM; Need ultrasonic)

Metabolic Enzyme/Protease

GSK2945 hydrochloride is a class of tertiary amine, and is a highly specific Rev-erbalpha/REV-ERBalpha (mouse/human reverse erythroblastosis virus alpha) antagonist with EC₅₀s of 21.5 uM and 20.8 uM, respectively. GSK2945 hydrochloride enhances cholesterol 7alpha-hydroxylase (CYP7A1) level and cholesterol metabolism^[1]. In Vitro: GSK2945 dose-dependently enhances the transcriptional activity of Rev-erbalpha and a Bmal1 (a target gene of REV-ERBs) luciferase reporter (EC₅₀ of 2.05 uM)^[1].
GSK2945 (20 uM; 12 hours and 24 hours; mouse and human primary hepatocytes) treatment increases levels of Cyp7a1/CYP7A1 in mouse and human primary hepatocytes. GSK2945 (20 uM) treatment also increases Lrh-1/LRH-1 (a known hepatic activator of Cyp7a1/CYP7A1) mRNA and protein^[1]. In Vivo: GSK2945 (0-10 mg/kg; intraperitoneal injection; twice every day; for 7 days; male C57BL/6 mice) treatment increases hepatic mouse cholesterol 7alpha-hydroxylase (Cyp7a1) level and lowers plasma cholesterol in wild-type mice^[1].