Comparison of the ligand binding site of CYP2C8 with CYP26A1 and CYP26B1: a structural basis for the identification of new inhibitors of the retinoic acid hydroxylases.

ABSTRACT: The CYP26s are responsible for metabolizing retinoic acid and play an important role in maintaining homeostatic levels of retinoic acid. Given the ability of CYP2C8 to metabolize retinoic acid, we evaluated the potential for CYP2C8 inhibitors to also inhibit CYP26. In vitro assays were used to evaluate the inhibition potencies of CYP2C8 inhibitors against CYP26A1 and CYP26B1. Using tazarotenic acid as a substrate for CYP26, IC₅₀ values for 17 inhibitors of CYP2C8 were determined for CYP26A1 and CYP26B1, ranging from ∼20 nM to 100 μM, with a positive correlation observed between IC₅₀s for CYP2C8 and CYP26A1. An evaluation of IC₅₀'s versus in vivo C_max values suggests that inhibitors such as clotrimazole or fluconazole may interact with CYP26 at cl

SUBMITTER: Foti RS 

PROVIDER: S-EPMC6628712 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature