SMARCA2 degrader

SMARCA2 degrader is a selective targeted protein degradation (TPD) agent developed by Aurigene Oncology Limited to treat cancers with SMARCA4 (BRG1) mutations. The drug utilizes a bivalent molecule (PROTAC) design, consisting of a SMARCA2-selective bromodomain binder linked to an E3 ubiquitin ligase ligand. This configuration facilitates the recruitment of an E3 ligase to the SMARCA2 protein, leading to its ubiquitination and subsequent degradation by the proteasome. The therapeutic strategy relies on synthetic lethality: in SMARCA4-deficient tumors, the loss of the primary SWI/SNF ATPase subunit creates a critical dependency on the paralog SMARCA2. Degrading SMARCA2 in these cells disrupts chromatin remodeling and inhibits tumor growth. The program has produced a lead intravenous (IV) candidate with a long-acting formulation (administered once every four weeks) for which the US FDA has accepted an IND application, as well as orally bioavailable analogs currently in preclinical development.

Other names

SMARCA2 selective degraderSMARCA-2 selective degraderSMARCA 2 selective degraderBRM degrader