MM-401

MM-401 is a macrocyclic peptidomimetic small molecule inhibitor designed to target the Mixed Lineage Leukemia 1 (MLL1) histone H3K4 methyltransferase complex. It specifically functions by disrupting the protein-protein interaction between MLL1 and its essential regulatory cofactor, WD Repeat Domain 5 (WDR5), by binding to the WDR5-interaction (Win) motif site. This inhibition prevents the assembly of the active MLL1 methyltransferase complex, thereby reducing histone H3K4 methylation levels. Developed initially at the University of Michigan and later by Merrimack Pharmaceuticals, MM-401 was primarily investigated for the treatment of MLL-rearranged acute leukemias, where it demonstrated the ability to induce cell cycle arrest, apoptosis, and myeloid differentiation in preclinical models. Development of the compound has since been discontinued at the preclinical stage.