A 2024 Update on Menin Inhibitors. A New Class of Target Agents against KMT2A-Rearranged and NPM1-Mutated Acute Myeloid Leukemia

IF 16.4 1区化学 Q1 CHEMISTRY, MULTIDISCIPLINARY

Accounts of Chemical Research Pub Date : 2024-04-18 DOI:10.3390/hematolrep16020024

A. Candoni, Gabriele Coppola

引用次数: 0

Abstract

Menin inhibitors are new and promising agents currently in clinical development that target the HOX/MEIS1 transcriptional program which is critical for leukemogenesis in histone-lysine N-methyltransferase 2A-rearranged (KMT2Ar) and in NPM1-mutated (NPM1mut) acute leukemias. The mechanism of action of this new class of agents is based on the disruption of the menin–KMT2A complex (consisting of chromatin remodeling proteins), leading to the differentiation and apoptosis of AML cells expressing KMT2A or with mutated NPM1. To date, this new class of drugs has been tested in phase I and II clinical trials, both alone and in combination with synergistic drugs showing promising results in terms of response rates and safety in heavily pre-treated acute leukemia patients. In this brief review, we summarize the key findings on menin inhibitors, focusing on the mechanism of action and preliminary clinical data on the treatment of acute myeloid leukemia with this promising new class of agents, particularly revumenib and ziftomenib.

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梅宁抑制剂的 2024 年最新进展。抗击 KMT2A 重排和 NPM1 突变急性髓性白血病的新型靶向药物

Menin抑制剂是目前处于临床开发阶段的新型药物，它以HOX/MEIS1转录程序为靶点，而HOX/MEIS1转录程序对于组蛋白-赖氨酸N-甲基转移酶2A重排（KMT2Ar）和NPM1突变（NPM1mut）急性白血病的白血病发生至关重要。这一类新药的作用机理是破坏 menin-KMT2A 复合物（由染色质重塑蛋白组成），导致表达 KMT2A 或 NPM1 突变的急性髓细胞分化和凋亡。迄今为止，这一类新药已在 I 期和 II 期临床试验中进行了测试，无论是单独使用还是与增效药物联合使用，都显示出对接受过大量预处理的急性白血病患者在应答率和安全性方面的良好效果。在这篇简短的综述中，我们将总结有关 menin 抑制剂的主要研究成果，重点介绍这一类前景广阔的新药（尤其是 revumenib 和 ziftomenib）治疗急性髓性白血病的作用机制和初步临床数据。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Accounts of Chemical Research 化学-化学综合

CiteScore

31.40

自引率

1.10%

发文量

312

审稿时长

2 months

期刊介绍： Accounts of Chemical Research presents short, concise and critical articles offering easy-to-read overviews of basic research and applications in all areas of chemistry and biochemistry. These short reviews focus on research from the author’s own laboratory and are designed to teach the reader about a research project. In addition, Accounts of Chemical Research publishes commentaries that give an informed opinion on a current research problem. Special Issues online are devoted to a single topic of unusual activity and significance. Accounts of Chemical Research replaces the traditional article abstract with an article "Conspectus." These entries synopsize the research affording the reader a closer look at the content and significance of an article. Through this provision of a more detailed description of the article contents, the Conspectus enhances the article's discoverability by search engines and the exposure for the research.