HM100760

HM100760 is a potent and selective small molecule inhibitor of Methionine adenosyltransferase 2A (MAT2A), currently under preclinical development by Hanmi Pharmaceutical. MAT2A is the primary enzyme responsible for the synthesis of S-adenosylmethionine (SAM) from methionine and ATP. In cancers harboring deletions of the methylthioadenosine phosphorylase (MTAP) gene—which occurs in approximately 15% of all human cancers—the accumulation of methylthioadenosine (MTA) partially inhibits PRMT5. HM100760 further reduces intracellular SAM levels, sensitizing PRMT5 to inhibition and leading to a synthetic lethal effect. Preclinical data presented at AACR 2025 demonstrated that HM100760 exhibits robust anti-proliferative activity across various MTAP-deficient cancer cell lines, including pancreatic, bladder, and non-small cell lung cancer (NSCLC). In vivo studies showed dose-dependent tumor growth inhibition in multiple xenograft models and synergistic efficacy when combined with PRMT5 inhibitors, maintaining a favorable safety profile.