WD-repeat protein 5 (WDR5) is a scaffold protein commonly involved in the formation of nucleosome-modifying protein complexes with histones.1 It serves as a component of a mixed-lineage leukemia (MLL) methyltransferase complex that targets histone 3 at lysine 4 to upregulate transcription.2 MM-102 is a potent WDR5/MLL interaction inhibitor (IC50 = 2.4 nM).3 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.3 MM-102 can also inhibit cell growth and induce apoptosis in leukemia cells harboring MLL1 fusion proteins.3
1.Migliori, V., Mapelli, M., and Guccione, E.On WD40 proteins: Propelling our knowledge of transcriptional control?Epigenetics7(8)815-822(2012) 2.Guccione, E., Bassi, C., Casadio, F., et al.Methylation of histone H3R2 by PRMT6 and H3K4 by an MLL complex are mutually exclusiveNature449(7164)933-937(2007) 3.Karatas, H., Townsend, E.C., Cao, F., et al.High-affinity, small-molecule peptidomimetic inhibitors of MLL1/WDR5 protein-protein interactionJ. Am. Chem. Soc.135(2)669-682(2013)