DS-437

DS-437 is a potent and selective small-molecule inhibitor of Protein Arginine Methyltransferase 5 (PRMT5) and Protein Arginine Methyltransferase 7 (PRMT7). Developed as a chemical probe by the Structural Genomics Consortium (SGC), it acts as a substrate-competitive inhibitor, blocking the symmetric dimethylation of arginine residues on both histone and non-histone proteins. PRMT5 is frequently overexpressed in various cancers and is involved in promoting cell proliferation, survival, and metabolic reprogramming. In preclinical studies, DS-437 has demonstrated the ability to inhibit the growth of cancer cells and overcome resistance to standard therapies, such as gemcitabine in pancreatic ductal adenocarcinoma (PDAC), by modulating the UBR7-PRMT5 axis and reducing glycolysis.