OPN-9652

OPN-9652 is an orally active, covalent small molecule inhibitor targeting the TEA domain (TEAD) family of transcription factors. It is designed to bind covalently to the central palmitate-binding pocket of TEAD proteins, specifically modifying Cys359 on TEAD1. This mechanism disrupts TEAD-dependent transcription, which plays a critical role in tumor growth and resistance in cancers with dysregulated Hippo pathway signaling—such as those harboring neurofibromatosis 2 (NF2) mutations. Preclinical studies have demonstrated that OPN-9652 exhibits potent anti-tumor activity as both monotherapy and in combination with other agents (e.g., trametinib), showing significant tumor growth inhibition and synergistic effects on downstream gene targets. The drug has shown potential for blood-brain barrier penetration and favorable tolerability profiles in animal models[1][4][5][7].