HD-11030

HD-11030 is a selective small molecule inhibitor of SMARCA2 (also known as BRM), developed by Hyundai Pharm for the treatment of SMARCA4-mutated cancers. SMARCA2 and SMARCA4 are mutually exclusive catalytic ATPase subunits of the BAF (SWI/SNF) chromatin remodeling complex. In cancers where SMARCA4 is deficient or mutated—a common occurrence in approximately 10% of non-small cell lung cancers (NSCLC) and other solid tumors—cells become synthetically lethal and dependent on the paralog SMARCA2 for survival. HD-11030 binds to the ATPase domain of SMARCA2 with single-digit nanomolar potency and demonstrates over 30-fold selectivity against SMARCA4. Preclinical evaluations in SMARCA4-mutant xenograft models, such as SK-MEL-5 melanoma and A549 NSCLC, have demonstrated that oral administration of HD-11030 leads to dose-dependent tumor growth arrest and regression.