1 research outputs found
Discovery of the Selective CYP17A1 Lyase Inhibitor BMS-351 for the Treatment of Prostate Cancer
Efforts to identify a potent, reversible,
nonsteroidal CYP17A1
lyase inhibitor with good selectivity over CYP17A1 hydroxylase and
CYPs 11B1 and 21A2 for the treatment of castration-resistant prostate
cancer (CRPC) culminated in the discovery of BMS-351 (compound <b>18</b>), a pyridyl biaryl benzimidazole with an excellent <i>in vivo</i> profile. Biological evaluation of BMS-351 at a dose
of 1.5 mg in castrated cynomolgus monkeys revealed a remarkable reduction
in testosterone levels with minimal glucocorticoid and mineralcorticoid
perturbation. Based on a favorable profile, BMS-351 was selected as
a candidate for further preclinical evaluation