Recent Progress of Small Molecule Menin–MLL Interaction Inhibitors as Therapeutic Agents for Acute Leukemia
Hao Lei, San‐Qi Zhang, Shu Fan, Huanrong Bai, Hongyi Zhao, Shuai Mao, Minhang Xin
Abstract
Mixed lineage leukemia (MLL) gene rearrangements are associated with acute leukemia. The protein menin is regarded as a critical oncogenic cofactor of the resulting MLL fusion proteins in acute leukemia. A direct interaction between menin and the MLL amino terminal sequences is necessary for MLL fusion protein-mediated leukemogenesis. Thus, inhibition of the interaction between menin and MLL has emerged as a novel therapeutic strategy. Recent improvements in structural biology and chemical reactivity have promoted the design and development of selective and potent menin-MLL interaction inhibitors. In this Perspective, different classes of menin-MLL interaction inhibitors are comprehensively summarized. Further research potential, challenges, and opportunities in the field are also discussed.