Human sterol 14α-demethylase as a target for anticancer chemotherapy: towards structure-aided drug design.

ABSTRACT: Rapidly multiplying cancer cells synthesize greater amounts of cholesterol to build their membranes. Cholesterol-lowering drugs (statins) are currently in clinical trials for anticancer chemotherapy. However, given at higher doses, statins cause serious side effects by inhibiting the formation of other biologically important molecules derived from mevalonate. Sterol 14α-demethylase (CYP51), which acts 10 steps downstream, is potentially a more specific drug target because this portion of the pathway is fully committed to cholesterol production. However, screening a variety of commercial and experimental inhibitors of microbial CYP51 orthologs revealed that most of them (including all clinical antifungals) weakly inhibit human CYP51 activity, even if they display high apparent spectral bind

SUBMITTER: Hargrove TY 

PROVIDER: S-EPMC4959870 | biostudies-literature | 2016 Aug

REPOSITORIES: biostudies-literature