WD-repeat protein 5 (WDR5) is a scaffold protein commonly involved in the formation of nucleosome-modifying protein complexes with histones. It serves as a component of a mixed-lineage leukemia (MLL) methyltransferase complex that targets histone 3 at lysine 4 to upregulate transcription. MM-102 is a potent WDR5/MLL interaction inhibitor (IC50 = 2.4 nM). It has been shown to block MLL1 methyltransferase activity, reducing the expression of HoxA9 and Meis-1 genes, which are both critical MLL1 target genes in MLL1 fusion protein-mediated leukemogenesis. MM-102 can also inhibit cell growth and induce apoptosis in leukemia cells harboring MLL1 fusion proteins.
