Inhibition of cholesterol biosynthesis in vitro by beta-diethylaminoethyl diphenylpropylacetate hydrochloride (SKF 525-A).

P-Diethylaminoethyl diphenylpropylacetate hydrochloride (SKF 525-A) has been shown to inhibit a number of reactions involved in drug metabolism (1)) including side-chain oxidation, dealkylation, deamination, hydrosylation, and deesterification. More recently this compound was found to decrease significantly the plasma cholesterol levels in several animal species (2). However, these studies afforded no information concerning the possible mechanism whereby this compound produced its hypocholesterolemic effect. In the experiments reported here, this drug has been found to inhibit the conversion of mevalonate-2-Cl4 to cholesterol. It also interfered with the incorporation of this substrate into other nonsaponifiable lipids, but it did not affect the decarboxylation of mevalonate-1-Ci4. These data suggest that the site of inhibition lies between isopentenyl pyrophosphate and squalene on the biosynthetic pathway leading to cholesterol.