Effect of FR194738, a potent inhibitor of squalene epoxidase, on cholesterol metabolism in HepG2 cells

• Published in: European journal of pharmacology Vol. 431; no. 1; pp. 11 - 16
• Main Authors: Sawada, Masae, Matsuo, Masahiko, Hagihara, Hiroyuki, Tenda, Noriko, Nagayoshi, Akira, Okumura, Hiroyuki, Washizuka, Ken-ichi, Seki, Jiro, Goto, Toshio
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 09.11.2001; Elsevier
• Subjects: Benzylamines - pharmacology; Biological and medical sciences; Cholesterol - biosynthesis; Cholesterol - metabolism; Enzyme Inhibitors - pharmacology; FR194738; General and cellular metabolism. Vitamins; HepG2 cell; HMG-CoA reductase; Humans; Hydroxymethylglutaryl CoA Reductases - isolation & purification; Hydroxymethylglutaryl CoA Reductases - metabolism; Hydroxymethylglutaryl-CoA Reductase Inhibitors - pharmacology; Medical sciences; Molecular Structure; Oxygenases - antagonists & inhibitors; Pharmacology. Drug treatments; Simvastatin; Simvastatin - analogs & derivatives; Simvastatin - pharmacology; Squalene - metabolism; Squalene epoxidase; Squalene Monooxygenase; Tumor Cells, Cultured; HMG-CoA reductase; HepG2 cell; FR194738; Squalene epoxidase; Simvastatin; Squalene monooxygenase; Enzyme; Hydroxymethylglutaryl-CoA synthase; Enzyme inhibitor; Lyases; Statin derivative; Metabolism; In vitro; Biological activity; Cholesterol; Oxo-acid-lyases; Carbon-carbon lyases; Enzymatic activity; Hepatocyte; Established cell line; Oxidoreductases; Intracellular; Mechanism of action; Comparative study; Antilipemic agent

( E)- N-ethyl- N-(6,6-dimethyl-2-hepten-4-ynyl)-3-[2-methyl-2-(3-thienylmethoxy)propyloxy]benzylamine hydrochloride (FR194738) inhibited squalene epoxidase activity in HepG2 cell homogenates with an IC 50 value of 9.8 nM. In the study using intact HepG2 cells, FR194738 inhibited cholesterol synthesi...