MLL1-WDR5相互作用抑制剂的研究进展

Research Progress on Small Molecule Inhibitors of MLL1-WDR5 Interaction

MLL1是选择性催化组蛋白H3第4位赖氨酸甲基化的甲基转移酶,可以调控多种在胚胎发育和血细胞分化中有重要功能基因的表达。MLL1-WDR5结合对MLL1的甲基转移酶活性至关重要,因此阻断MLL1与WDR5相互作用是抑制MLL1的甲基转移酶活性的有效方法。本文介绍了近几年抑制MLL1-WDR5相互作用小分子化合物的研究进展,并对这类化合物的研究前景进行了展望。

Mixed lineage leukemia 1 （MLLI） is a methyltransferase which can specifically catalyze the methylation of the lysine 4 in histone 3 （H3K4） and regulate the expression of many genes involved in embryonic development and haematologica differentiation. The MLL1-WDR5 protein-protein interaction is essential for the enzymatic activity of MLL1, therefore blockage of the interaction between MLL1 and WDR5 is an effective strategy to inhibit the methyltransferase activity of MLL1. In this review, we introduced the recent progress for the development of small molecular compounds which can inhibit the interaction between MLLI and WDRS.