FR901512, a novel HMG-CoA reductase inhibitor produced by an agonomycetous fungus no. 14919. II. Biological profiles.
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.
Exploratory Research Laboratories, Fujisawa Pharmaceutical Co., Ltd., 5-2-3 Tokodai, Tsukuba, Ibaraki 300-2698, Japan. hidetaka_hatori@po.fujisawa.co.jp
Hidetaka
H
Hatori
Bunji
B
Sato
Ikuko
I
Sato
Toshihiro
T
Shibata
Hirotsugu
H
Ueda
Motohiro
M
Hino
Takashi
T
Fujii
D000818:Animals; D000924:Anticholesteremic Agents / Q000378:metabolism / Q000494:pharmacology; D045744:Cell Line, Tumor; D002784:Cholesterol / Q000097:blood; D004285:Dogs; D005658:Fungi / Q000378:metabolism*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000378:metabolism / Q000494:pharmacology*; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051381:Rats; D011973:Receptors, LDL / Q000378:metabolism; D013261:Sterols / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D013764:Tetrahydronaphthalenes / Q000378:metabolism / Q000494:pharmacology*; D015854:Up-Regulation
D000924:Anticholesteremic Agents; C487955:FR901512; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D011973:Receptors, LDL; D013261:Sterols; D013764:Tetrahydronaphthalenes; D002784:Cholesterol