P9i

P9i is an experimental, small molecule inhibitor of protein arginine N-methyltransferase 9 (PRMT9). Developed by researchers at the City of Hope and Fujian Medical University, P9i is designed to overcome resistance to the BCL-2 inhibitor venetoclax in acute myeloid leukemia (AML). PRMT9 is a methyltransferase that regulates RNA splicing and protein translation. Inhibition of PRMT9 by P9i leads to aberrant splicing of transcripts like ALG13 and suppresses the translation of short-lived proteins, including the pro-survival factor MCL1. In preclinical models, P9i has demonstrated the ability to sensitize venetoclax-resistant AML cells to apoptosis and significantly extend survival when used in combination with venetoclax and azacitidine.