Schizostatin, a novel squalene synthase inhibitor produced by the mushroom, Schizophyllum commune. I. Taxonomy, fermentation, isolation, physico-chemical properties and biological activities.
In the process of screening for squalene synthase inhibitors from microbial fermentation products we have isolated a novel compound, named schizostatin (Fig. 1), from the culture broth of the mushroom, Schizophyllum commune SANK 17785. Schizostatin inhibited rat liver microsomal squalene synthase dose dependently and the IC50 value was 0.84 microM. The inhibition was competitive with respect to farnesylpyrophosphate with a Ki value of 0.45 microM.
Tanimoto
T
T
Pharmacology and Molecular Biology Research Laboratories, Sankyo Co., Ltd., Tokyo, Japan.
Onodera
K
K
Hosoya
T
T
Takamatsu
Y
Y
Kinoshita
T
T
Tago
K
K
Kogen
H
H
Fujioka
T
T
Hamano
K
K
Tsujita
Y
Y
D019883:Alkyl and Aryl Transferases; D000818:Animals; D000890:Anti-Infective Agents / Q000494:pharmacology; D002478:Cells, Cultured; D002784:Cholesterol / Q000096:biosynthesis; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D013186:Farnesyl-Diphosphate Farnesyltransferase / Q000037:antagonists & inhibitors*; D005227:Fatty Acids / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D005650:Fumarates / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D008099:Liver / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D008826:Microbial Sensitivity Tests; D051381:Rats; D017208:Rats, Wistar; D012567:Schizophyllum / Q000737:chemistry / Q000378:metabolism* / Q000502:physiology; D014166:Transferases / Q000037:antagonists & inhibitors
D000890:Anti-Infective Agents; D004791:Enzyme Inhibitors; D005227:Fatty Acids; D005650:Fumarates; C101437:schizostatin; D002784:Cholesterol; D014166:Transferases; D019883:Alkyl and Aryl Transferases; C064911:p21(ras) farnesyl-protein transferase; D013186:Farnesyl-Diphosphate Farnesyltransferase