MS177

MS177 is a first-in-class, dual-action proteolysis targeting chimera (PROTAC) designed to induce the degradation of both the histone methyltransferase EZH2 (Enhancer of zeste homolog 2) and the MYC oncoprotein. Developed through a collaboration between the Icahn School of Medicine at Mount Sinai and the University of North Carolina at Chapel Hill, MS177 was specifically engineered to address resistance in acute myeloid leukemia (AML), particularly in patients who fail to respond to hypomethylating agents (HMAs). By concurrently targeting the EZH2-MYC axis, MS177 disrupts key epigenetic and oncogenic signaling pathways that drive leukemogenesis and therapeutic resistance. Preclinical studies have demonstrated that MS177 exhibits potent cytotoxicity in AML cell lines and patient-derived tumor samples, showing significantly greater efficacy in HMA-resistant phenotypes compared to standard treatments such as azacitidine.