The Profile of an HMG-CoA Reductase Inhibitor, CS-514 (SQ 31,000)
Since more than 70% of the total input of body cholesterol is derived from de novo synthesis in humans (Dietschy and Wilson 1970), it is expected that the high level of serum cholesterol can be reduced in consequence of inhibition of cholesterol synthesis. The most desirable target for this inhibition is 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, the rate-limiting enzyme of cholesterogenesis. ML-236B (also called compactin) was discovered first by Sankyo Co. from the culture broth of a microorganism as a potent competitive inhibitor of HMG-CoA reductase (Endo et al. 1976), and showed remarkable hypolipidemic effect on various experimental animals as well as humans (Kuroda et al. 1979; Tsujita et al. 1979; Yamamoto et al. 1980).
KeywordsFamilial Hypercholesterolemia Sterol Synthesis Hypolipidemic Effect Aortic Atherosclerosis WHHL Rabbit
Unable to display preview. Download preview PDF.
- Tsujita Y, Kuroda M, Shimada Y, Tanzawa K, Arai M, Kaneko I, Tanaka M, Masuda H, Tarumi C, Watanabe Y, Fujii S (1986) CS-514, a competitive inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase: tissue-selective inhibition of sterol synthesis and hypolipidemic effect on various animal species. Biochim Biophys Acta 877:50–60PubMedGoogle Scholar