Discovery of maleimide derivatives as m6A demethylase ALKBH5 inhibitors

IF 3.3 3区医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Bioorganic & Medicinal Chemistry Pub Date : 2025-01-27 DOI:10.1016/j.bmc.2025.118083

Luxia Liang , Wenlong Fei , Yingzhe Wang , Ze Zhang , Qidong You , Xiaoke Guo

引用次数: 0

Abstract

Human AlkB homologue H5 (ALKBH5) is a crucial demethylase for N⁶-methyladenosine (m⁶A) of mRNA. Although ALKBH5 is recognized as a promising target in various cancers, especially acute myeloid leukemia (AML), research on inhibitors of ALKBH5 remains limited. Here, we reported the discovery of a series of maleimide-based small molecule inhibitors of ALKBH5, resulting in the identification of compound 18 through optimization. Comprehensive evaluations suggested that compound 18 holds significant potential as a lead compound for ALKBH5 inhibitor.

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来源期刊

Bioorganic & Medicinal Chemistry 医学-生化与分子生物学

CiteScore

6.80

自引率

2.90%

发文量

413

审稿时长

17 days

期刊介绍： Bioorganic & Medicinal Chemistry provides an international forum for the publication of full original research papers and critical reviews on molecular interactions in key biological targets such as receptors, channels, enzymes, nucleotides, lipids and saccharides. The aim of the journal is to promote a better understanding at the molecular level of life processes, and living organisms, as well as the interaction of these with chemical agents. A special feature will be that colour illustrations will be reproduced at no charge to the author, provided that the Editor agrees that colour is essential to the information content of the illustration in question.