1438071-12-5 N-[(4-氯-2-甲基苯基)甲基]-1-(4-氯苯基)-N-[(5-硝基噻吩-2-基)甲基]甲胺

• 生物活性 GSK2945 是一类叔胺，是一种高度特异性的 Rev-erbα/REV-ERBα (小鼠/人反向成红细胞病病毒α) 拮抗剂， 其 EC50 值分别为 21.5 μM 和 20.8 μM。GSK2945 可增强胆固醇 7α-羟化酶 (CYP7A1) 水平和胆固醇代谢。
• 体外研究 GSK2945 dose-dependently enhances the transcriptional activity of Rev-erbα and a Bmal1 (a target gene of REV-ERBs) luciferase reporter ( EC 50 of 2.05 μM). 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. RT-PCR Cell Line: Mouse (male, CD1) and human (male, Caucasian) primary hepatocytes Concentration: 20 μM Incubation Time: 12 hours and 24 hours Result: Led to significant increases in mRNA and protein (at 24-h) expression of Cyp7a1. mRNA and protein (at 24-h) levels of CYP7A1 were increased in human primary hepatocyte. Lrh-1/LRH-1 was upregulated.
• 体内研究 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. Animal Model: Male C57BL/6 mice (8-10 weeks of age) Dosage: 0 mg/kg or 10 mg/kg Administration: Intraperitoneal injection; twice every day; for 7 days Result: Increased hepatic mouse cholesterol 7α-hydroxylase (Cyp7a1) level and lowered plasma cholesterol in wild-type mice.

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