BMS-501949

BMS-501949 is a **small molecule metabolite** formed from BMS-641988, a nonsteroidal antiandrogen developed by Bristol Myers Squibb primarily for the treatment of prostate cancer. BMS-641988 is metabolized first to BMS-570511 by CYP3A4, which is then reduced to BMS-501949 by cytosolic reductases[5][1]. BMS-501949, along with its precursor and parent compound, displays antiandrogenic activity by antagonizing the androgen receptor. However, BMS-501949 is also associated with the induction of seizures in preclinical animal models, a side effect attributed to its activity as a negative allosteric modulator (inhibitor) of the GABA-A receptor[5][1][11][7]. The compound readily crosses the blood-brain barrier. Clinical development of the parent compound (and thus its metabolites) was halted due to limited anti-tumor efficacy and a significant risk of neurotoxicity (seizures)[1][7][13]. BMS-501949 itself was characterized mainly in preclinical safety studies.