GH37

GH37 is a small molecule inhibitor of Methionine Adenosyltransferase 2A (MAT2A) being developed by Suzhou Genhouse Bio for the treatment of MTAP-deleted solid tumors. MAT2A is the primary enzyme responsible for the synthesis of S-adenosylmethionine (SAM), the universal methyl donor. In cancers where the Methylthioadenosine Phosphorylase (MTAP) gene is deleted (a common occurrence due to its proximity to the CDKN2A locus), the metabolite methylthioadenosine (MTA) accumulates and partially inhibits PRMT5. GH37-mediated inhibition of MAT2A further depletes SAM levels, leading to a profound and selective reduction in PRMT5 activity and subsequent cell death in MTAP-deficient cells, a concept known as synthetic lethality.