TM-7

TM-7 is a small molecule inhibitor that targets the YEATS domain of the ENL (Ear-Two-Like) protein and its paralogue AF9. Developed by researchers at Scripps Research, TM-7 is primarily investigated for its potential in treating acute myeloid leukemia (AML), particularly subtypes characterized by KMT2A (MLL) rearrangements or partial tandem duplications (KMT2A-PTD). By binding to the YEATS domain, TM-7 disrupts the interaction between ENL/AF9 and acetylated histones, which leads to the displacement of the super-elongation complex (SEC) and DOT1L from chromatin. This mechanism results in the downregulation of critical oncogenic driver genes, including HOXA9 and MYC. In preclinical models, TM-7 has demonstrated the ability to induce differentiation and reduce leukemia burden, especially when used in synergistic combination with menin inhibitors such as revumenib.