BRSD056

BRSD056 is a potent small molecule degrader targeting the paralog histone acetyltransferases p300 (EP300) and CBP (CREBBP). It functions as a proteolysis-targeting chimera (PROTAC) that induces cereblon (CRBN)-mediated ternary complex formation, leading to the ubiquitination and subsequent proteasomal degradation of p300 and CBP. These enzymes are essential co-activators for transcription factors such as the Androgen Receptor (AR) and c-Myc, which drive the progression of castration-resistant prostate cancer (CRPC). By degrading these targets, BRSD056 inhibits cell growth and modulates key oncogenic proteins including AR, c-Myc, and FOXA1. To overcome hematologic toxicities associated with systemic p300/CBP inhibition, BRSD056 has been vectorized as a payload in antibody-drug conjugates (ADCs) targeting prostate cancer antigens such as B7H3 and PSMA, allowing for localized delivery and improved therapeutic index.