GH-31

GH-31 is a potent and selective oral small-molecule inhibitor of methionine adenosyltransferase 2A (MAT2A), currently in preclinical development by Genhouse Bio. It is designed to treat cancers characterized by the deletion of methylthioadenosine phosphorylase (MTAP), a genetic alteration found in approximately 10-15% of all human tumors, including glioblastoma, mesothelioma, and pancreatic cancer. GH-31 leverages the principle of synthetic lethality; in MTAP-deleted cells, the accumulation of methylthioadenosine (MTA) creates a vulnerability that MAT2A inhibition exploits by further depleting S-adenosylmethionine (SAM) levels, leading to selective tumor cell death. Notably, GH-31 exhibits significant brain-to-plasma distribution (Kpuu > 0.6), making it a promising candidate for primary brain tumors and central nervous system metastases.