BMS-641988

BMS-641988 is a novel, oral, nonsteroidal androgen receptor antagonist developed by Bristol-Myers Squibb for the treatment of prostate cancer, specifically castration-resistant prostate cancer (CRPC). It acts as a potent competitive antagonist of the androgen receptor (AR), with significantly higher binding affinity and antiandrogenic activity than bicalutamide. In preclinical models, BMS-641988 demonstrated strong inhibition of AR signaling and superior efficacy in tumor growth inhibition compared to standard antiandrogens. The drug also exhibits some weak partial agonist activity at the AR and is metabolized into active metabolites with similar pharmacological profiles. Additionally, BMS-641988 has been shown to act as a negative allosteric modulator of the GABA_A_ receptor at high doses, which can lead to seizures—a side effect that contributed to discontinuation of its clinical development after phase I trials due to safety concerns and limited antitumor activity[3][5][6][10].