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Current Medicinal Chemistry


ISSN (Print): 0929-8673
ISSN (Online): 1875-533X

Review Article

The Development of Inhibitors Targeting the Mixed Lineage Leukemia 1 (MLL1)-WD Repeat Domain 5 Protein (WDR5) Protein- Protein Interaction

Author(s): Xiaoqing Ye, Gang Chen, Jia Jin, Binzhong Zhang, Yinda Wang, Zhenhai Cai and Fei Ye*

Volume 27 , Issue 33 , 2020

Page: [5530 - 5542] Pages: 13

DOI: 10.2174/0929867326666190528080514

Price: $65


Mixed Lineage Leukemia 1 (MLL1), an important member of Histone Methyltransferases (HMT) family, is capable of catalyzing mono-, di-, and trimethylation of Histone 3 lysine 4 (H3K4). The optimal catalytic activity of MLL1 requires the formation of a core complex consisting of MLL1, WDR5, RbBP5, and ASH2L. The Protein-Protein Interaction (PPI) between WDR5 and MLL1 plays an important role in abnormal gene expression during tumorigenesis, and disturbing this 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 of inhibitors targeting MLL1- WDR5 interaction.

Keywords: WDR5, MLL1, histone methyltransferase, small-molecular inhibitor, epigenetics, human acute leukemia.

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