HD-11273

HD-11273 is a selective small molecule inhibitor of SMARCA2 (also known as BRM), the catalytic ATPase subunit of the SWI/SNF chromatin remodeling complex. Developed by Hanon Therapeutics, HD-11273 is a specific salt form of the lead compound HD-10991, optimized for enhanced physicochemical properties. The therapeutic strategy for HD-11273 is based on the principle of synthetic lethality; it specifically targets cancer cells deficient in SMARCA4 (BRG1), a common mutation found in approximately 8-10% of non-small cell lung cancer (NSCLC) cases. By inhibiting the functional paralog SMARCA2 in the absence of SMARCA4, the drug disrupts essential gene regulation and chromatin dynamics, leading to tumor cell death. Preclinical studies have demonstrated that HD-11273 has significant monotherapy activity and exhibits robust synergy when combined with KRAS inhibitors (such as sotorasib, adagrasib, and pan-KRAS inhibitors) or standard chemotherapy agents like pemetrexed and docetaxel.