AR antagonist 15 is an orally active androgen receptor (AR) antagonist with an IC50 of 97 nM for ART787A. It impairs AR nuclear translocation, hinders AR homodimerization, and inhibits AR-regulated gene transcription by competitively binding to the ligand-binding pocket. AR antagonist 15 significantly reduces prostate-specific antigen (PSA) levels and induces apoptosis by decreasing the expression of apoptosis-related proteins. This compound is useful for prostate cancer research.

AR antagonist 15 (Compound LT16) exhibits significant antagonistic activity against the androgen receptor (AR) and its various mutations: AR T787A (IC50 = 97 nM), AR F877L (IC50 = 200 nM), AR F877L/T787A (IC50 = 260 nM), AR H875Y/T787A (IC50 = 200 nM), AR W742C (IC50 = 510 nM), and AR T787G (IC50 = 555 nM). It reduces prostate-specific antigen (PSA) secretion levels in a dose-dependent manner with an IC50 of 0.16 μM. AR antagonist 15 facilitates the translocation of AR from the cytoplasm to the nucleus over 48 hours, downregulates AR-regulated gene mRNA levels in LNCaP cells and significantly decreases mRNA levels of crucial proteins involved in apoptosis within the 0.1-10 μM concentration range for 48 hours. It also significantly inhibits the proliferation of AR-positive cells at concentrations of 0.01-100 μM over 3 to 5 days. Furthermore, at 10 μM for 48 hours, it induces G0/G1 cell cycle arrest in LNCaP cells. Additionally, in the range of 0.5-5 μM for 14 days, AR antagonist 15 inhibits LNCaP cell growth and reduces colony formation.

AR antagonist 15, administered at 50 mg/kg via intragastric route once daily for three weeks, significantly reduced tumor volume and lowered serum PSA levels in male Balb/C nude mice with prostate cancer.