PRT3879

PRT3879 is a first-in-class, potent, and selective small molecule degrader of SMARCA2 (also known as BRM), developed by Prelude Therapeutics. It utilizes a proteolysis-targeting chimera (PROTAC) approach to induce the degradation of SMARCA2, demonstrating over 20-fold selectivity over the closely related SMARCA4 (BRG1) protein. This selectivity is designed to exploit a synthetic lethal vulnerability in cancers where SMARCA4 is lost or mutated, such as in certain non-small cell lung cancers (NSCLC) and other solid tumors. In these SMARCA4-deficient cells, the survival of the cancer cell becomes dependent on the remaining SMARCA2 subunit of the BAF (SWI/SNF) chromatin remodeling complex. PRT3879 received IND clearance from the FDA in October 2022 and is currently being evaluated in Phase 1 clinical trials for patients with advanced or metastatic solid tumors harboring SMARCA4 mutations or deletions.