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The development of inhibitors targeting the Mixed lineage leukemia 1 (MLL1)-WD repeat domain 5 protein (WDR5) Protein-Protein Interaction.

Mixed lineage leukemia 1 (MLL1), an important member of histone methyltransferases (HMT) family, is closely associated with human acute leukemia. MLL1 could specially catalyze mono-, di-, and trimethylation of histone 3 lysine 4 (H3K4) via its conserved SET domain, the proper enzymatic activity depends on a core complex consisting of MLL1, WDR5, RbBP5, ASH2L and Dpy30. The protein-protein interaction (PPI) between WDR5 and MLL1 plays an important role in abnormal gene expression during tumorigenesis, disturbing MLL1-WDR5 interaction may have a potential for the treatment of leukemia harboring MLL1 fusion proteins. In this review, we will summarize recent progress in the development on inhibitors targeting MLL1-WDR5 interaction.