FR901512, a Novel HMG-CoA Reductase Inhibitor Produced by an Agonomycetous Fungus No. 14919

II. Biological Profiles

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 1.0nM. 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.