Section Review: Cardiovascular & Renal: Squalene epoxidase inhibitors

Abstract

Squalene epoxidase inhibitors represent an attractive target for the control of sterol biosynthesis. Success in the search for fungal squalene epoxidase inhibitors has led to commercial availability of drugs from this class (e.g., terbinafine from Sandoz). The discovery of NB-598, a potent and selective mammalian squalene epoxidase inhibitor able to decrease serum low density lipoprotein-cholesterol levels in dogs, with a similar potency to simvastatin, has stimulated increased efforts towards the identification of new mammalian squalene epoxidase inhibitors. Such compounds represent an attractive alternative to 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors as new therapeutic tools in the control of plasma low density lipoprotein-cholesterol levels, a major risk factor in coronary artery diseases. This article describes the recent development of this class of compounds, reviewing both the primary and patent literature.