1-hydroxy-3-(methylpentylamino)-propylidene-1,1-bisphosphonic acid as a potent inhibitor of squalene synthase

被引：0
|
作者：
Amin, D
Cornell, SA
Perrone, MH
Bilder, GE
机构：
来源：
ARZNEIMITTEL-FORSCHUNG/DRUG RESEARCH | 1996年 / 46卷 / 08期
关键词：
bisphosphonates; BM; 21.0955; pharmacology; squalene synthase inhibition; cholesterol; 1-hydroxy-3-(methylpentylamino)-propylidene 1,1-bisphosphonic acid; lipid reducers;
D O I：
暂无
中图分类号：
R914 [药物化学];
学科分类号：
100701 ;
摘要：
Squalene synthase, the first committed enzyme for sterol synthesis, converts farnesyl pyrophosphate to squalene with presqualene pyrophosphate as an intermediate. It was discovered that BM 21.0955 (1-hydroxy-3-(methylpentylamino)-propylidene-1,1-bisphosphonic acid), in development for the treatment of bone disorders, inhibited rat liver microsomal squalene synthase (K-i = 2 nmol/1). BM 21.0955 also inhibited sterol biosynthesis from mevalonate (IC50 = 42 nmol/l), and cholesterol biosynthesis in J774 cells (IC50 = 79 mu mol/1). Structural modifications on this molecule to make it more lipophilic may result in a new class of cholesterol-lowering agents.
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页码：759 / 762
页数：4
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