GSK2945 hydrochloride

• CAT Number: I046083
• Molecular Formula: C20H19Cl3N2O2S
• Molecular Weight: 457.80
• Purity: ≥95%
• Synonyms: N-[(4-chloro-2-methylphenyl)methyl]-1-(4-chlorophenyl)-N-[(5-nitrothiophen-2-yl)methyl]methanamine;hydrochloride
• InChI: InChI=1S/C20H18Cl2N2O2S.ClH/c1-14-10-18(22)7-4-16(14)12-23(11-15-2-5-17(21)6-3-15)13-19-8-9-20(27-19)24(25)26;/h2-10H,11-13H2,1H3;1H
• InChIKey: HRNMOPTYOFRUFF-UHFFFAOYSA-N
• SMILES: CC1=C(C=CC(=C1)Cl)CN(CC2=CC=C(C=C2)Cl)CC3=CC=C(S3)[N+](=O)[O-].Cl

GSK2945 hydrochloride 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 hydrochloride enhances cholesterol 7α-hydroxylase (CYP7A1) level and cholesterol metabolism[1].
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].
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].

Reference

[1]. Zhang T, et al. REV-ERBα Regulates CYP7A1 Through Repression of Liver Receptor Homolog-1. Drug Metab Dispos. 2018 Mar;46(3):248-258.
 [Content Brief]