GSK2945

GSK2945 is a class of tertiary amine, and is a highly specific Rev-erbα/REV-ERBα (mouse/human reverse erythroblastosis virus α) antagonist with EC₅₀s of 21.5 μM and 20.8 μM, respectively. GSK2945 enhances cholesterol 7α-hydroxylase (CYP7A1) level and cholesterol metabolism^[1]. In Vitro: GSK2945 dose-dependently enhances the transcriptional activity of Rev-erbα and a Bmal1 (a target gene of REV-ERBs) luciferase reporter (EC₅₀ of 2.05 μM)^[1].
GSK2945 (20 μM; 12 hours and 24 hours; mouse and human primary hepatocytes) treatment increases levels of Cyp7a1/CYP7A1 in mouse and human primary hepatocytes. GSK2945 (20 μM) 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 7α-hydroxylase (Cyp7a1) level and lowers plasma cholesterol in wild-type mice^[1].