FR901512, a novel HMG-CoA reductase inhibitor produced by an agonomycetous fungus no. 14919. II. Biological profiles

Hidetaka Hatori; Bunji Sato; Ikuko Sato; Toshihiro Shibata; Hirotsugu Ueda; Motohiro Hino; Takashi Fujii

doi:10.7164/antibiotics.57.390

FR901512, a novel HMG-CoA reductase inhibitor produced by an agonomycetous fungus no. 14919. II. Biological profiles

J Antibiot (Tokyo). 2004 Jun;57(6):390-3. doi: 10.7164/antibiotics.57.390.

Authors

Hidetaka Hatori¹, Bunji Sato, Ikuko Sato, Toshihiro Shibata, Hirotsugu Ueda, Motohiro Hino, Takashi Fujii

Affiliation

¹ Exploratory Research Laboratories, Fujisawa Pharmaceutical Co., Ltd., 5-2-3 Tokodai, Tsukuba, Ibaraki 300-2698, Japan. [email protected]

PMID: 15323128
DOI: 10.7164/antibiotics.57.390

Abstract

FR901512, a new specific inhibitor of HMG-CoA reductase, was isolated from the culture of an agonomycetous fungus No. 14919. FR901512 inhibited cholesterol synthesis from [14C] acetate in Hep G2 cells with an IC50 of 1.0 nM. An increase of cell surface LDL receptors observed on the FR901512 treated human hepatoma cell line Hep G2 cells. Single oral administration of FR901512 strongly inhibited sterol synthesis in rats. Daily oral administration of FR901512 to beagle dogs decreased plasma cholesterol levels.

MeSH terms

Animals
Anticholesteremic Agents / metabolism
Anticholesteremic Agents / pharmacology
Cell Line, Tumor
Cholesterol / blood
Dogs
Fungi / metabolism*
Humans
Hydroxymethylglutaryl-CoA Reductase Inhibitors / metabolism
Hydroxymethylglutaryl-CoA Reductase Inhibitors / pharmacology*
Liver / drug effects
Liver / metabolism
Male
Rats
Receptors, LDL / metabolism
Sterols / antagonists & inhibitors
Sterols / biosynthesis
Tetrahydronaphthalenes / metabolism
Tetrahydronaphthalenes / pharmacology*
Up-Regulation

Substances

Anticholesteremic Agents
FR901512
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Receptors, LDL
Sterols
Tetrahydronaphthalenes
Cholesterol