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

CS-514 is a tissue-selective inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase, a key enzyme in cholesterol synthesis. For the microsomal enzyme from rat liver, the mode of inhibition is competitive with respect to hydroxymethylglutaryl-CoA, and the Ki value is 2.3 X 10(-9) M. CS-514 also strongly inhibited the sterol synthesis from [14C]acetate in cell-free enzyme systems from rat liver and in freshly isolated rat hepatocytes; the...