PRP0004

PRP0004 is a potent, first-in-class small molecule degrader that targets both SMARCA2 and SMARCA4 proteins. It functions as a dual degrader, robustly inhibiting cancer cell growth and inducing apoptosis by promoting the degradation of these chromatin remodeling factors. Preclinical studies have shown that PRP0004 is highly effective in prostate cancer models, where it downregulates multiple oncogenic drivers and results in significant tumor cell death. However, as a monotherapy, it has demonstrated a narrow therapeutic window due to toxicity at higher doses. To address this limitation and improve tumor specificity while reducing off-target effects, PRP0004 has been conjugated to clinically validated antibodies (such as anti-PSMA), creating novel degrader antibody conjugates (DACs). These DACs achieve potent and antigen-selective internalization with robust SMARCA2/SMARCA4 degradation in various cancer types while being well-tolerated in preclinical models. This approach expands the potential application of SMARCA degraders beyond cancers with known SMARCA mutations[1][2][5][6][9].