NSC641396

NSC641396 is a small molecule inhibitor of protein arginine methyltransferase 9 (PRMT9) identified through structure-based virtual screening of the NCI and Zinc compound libraries. It is being investigated for its potential to treat acute myeloid leukemia (AML) by targeting leukemia stem cells (LSCs). The compound inhibits the catalytic activity of PRMT9, which is responsible for the methylation of poly(A) binding protein cytoplasmic 1 (PABP1) at the R493 residue. By blocking this methylation, NSC641396 disrupts the translational machinery that LSCs use to produce short-lived oncoproteins like c-Myc and Mcl-1, leading to decreased protein biosynthesis and increased apoptosis in AML cells.