The Tetrazole VT-1161 Is a Potent Inhibitor of Trichophyton rubrum through Its Inhibition of T. rubrum CYP51.

ABSTRACT: Prior to characterization of antifungal inhibitors that target CYP51, Trichophyton rubrum CYP51 was expressed in Escherichia coli, purified, and characterized. T. rubrum CYP51 bound lanosterol, obtusifoliol, and eburicol with similar affinities (dissociation constant [K_d ] values, 22.7, 20.3, and 20.9 μM, respectively) but displayed substrate specificity, insofar as only eburicol was demethylated in CYP51 reconstitution assays (turnover number, 1.55 min^-1; K_m value, 2 μM). The investigational agent VT-1161 bound tightly to T. rubrum CYP51 (K_d = 242 nM) with an affinity similar to that of clotrimazole, fluconazole, ketoconazole, and voriconazole (K_d values, 179, 173, 312, and 304 n

SUBMITTER: Warrilow AGS 

PROVIDER: S-EPMC5487648 | biostudies-literature | 2017 Jul

REPOSITORIES: biostudies-literature