Oxylanosterols as modifiers of cholesterol biosynthesis.
In this review, the thinking and strategy that lead to the design of mechanism-based inhibitors of cholesterol biosynthesis have been recounted. This work began with a purely biochemical perspective on the mechanism of lanosterol demethylation. The final efforts focused on pharmacology and drug design thus bringing the basic science effort to a practical application. Most recently, a series of 15-oxalanosterols, which act as pure suppressors of HMG-CoA reductase lacking lanosterol demethylase inhibition properties has been identified. These molecules also lower serum cholesterol and show promise as potential agents for clinical evaluation. The utility of these compounds and validation of our hypothesis will have to await further testing.
D001161:Arteriosclerosis / Q000188:drug therapy* / Q000378:metabolism; D002784:Cholesterol / Q000096:biosynthesis*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D006937:Hypercholesterolemia / Q000188:drug therapy* / Q000378:metabolism; D007810:Lanosterol / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism / Q000627:therapeutic use
D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D007810:Lanosterol; C050483:32-hydroxy-24,25-dihydrolanosterol; C032444:lanosten-3-ol-32-al; D002784:Cholesterol