A Cholesteryl Ester Transfer Protein Inhibitor from an Insect-associated Fungus.

The Journal of Antibiotics
1996.0

Abstract

Atherosclerosis is caused by the deposition of lipids, especially cholesterol, on to arterial walls, and continued lipid deposition leads to coronary heart disease.lf2) Epidemiological studies show the risk of coronary heart disease correlates with increased cholesterol levels associated with low-density lipoprotein (LDL) and inversely correlates with increased cholesterol levels associated with high-density lipoprotein (HDL).1'2) The transfer of cholesterol in the form of cholesteryl esters from HDLto LDLis mediated by cholesteryl ester transfer protein (CETP), a 66 ~ 77 kDa plasma glycoprotein.3) Studies have shown that CETP activity increases in the presence of a high fat, high cholesterol diet, and that individuals deficient in CETPactivity are usually resistant to atherosclerosis.3) CETP, which has been purified, cloned, and overexpressed in bacteria and Chinese hamster ovary cells, can conveniently be used in an in vitro assay system.4~6) Since CETPinhibitors could be important therapeutic agents, we began a program to search for such inhibitors among the secondary metabolites produced by fungi living in close association with plants and insects. In the course of this program, we detected a compoundwith CETPinhibitory activity from an insect-associated fungus.

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