Drugs and Scaffold That Inhibit Cytochrome P450 27A1 In Vitro and In Vivo.

ABSTRACT: Cytochrome P450 27A1 (CYP27A1) is a ubiquitous enzyme that hydroxylates cholesterol and other sterols. Complete CYP27A1 deficiency owing to genetic mutations is detrimental to human health, whereas 50% of activity retention is not and does not affect the whole body cholesterol levels. CYP27A1 is considered a potential therapeutic target in breast cancer and age-related neurodegenerative diseases; however, CYP27A1 inhibition should be ≤50%. Herein, 131 pharmaceuticals were tested for their effect on CYP27A1-mediated cholesterol 27-hydroxylation by in vitro enzyme assay. Of them, 14 drugs inhibited CYP27A1 by ≥75% and were evaluated for in vitro binding to the enzyme active site and for inhibition constants. All drugs except one (dasatinib) elicited a spectral response in CYP27A1 and had Ki

SUBMITTER: Lam M 

PROVIDER: S-EPMC5749491 | biostudies-literature | 2018 Feb

REPOSITORIES: biostudies-literature