ONC1-13B

ONC1-13B is a synthetic small molecule androgen receptor antagonist with antineoplastic activity. It specifically binds to the androgen receptor (AR), prevents AR activation and nuclear translocation, downregulates AR expression, and inhibits AR-mediated signaling. This results in inhibition of dihydrotestosterone (DHT)-stimulated prostate-specific antigen (PSA) expression and proliferation of prostate cancer cells. In preclinical models such as the LnCaP-Z2 xenograft model of prostate cancer, ONC1-13B demonstrated high efficacy in inhibiting tumor growth and suppressing PSA expression. Its mechanism of action is similar to that of enzalutamide (MDV3100) and apalutamide (ARN-509), but it shows lower brain distribution—suggesting a reduced risk for GABA-related seizures—and induces less CYP3A activity than these comparators, potentially reducing drug-drug interactions. The drug has been evaluated in clinical trials for metastatic castration-resistant prostate cancer[1][2][4][5][6][7].