Menin-MLL protein-protein interaction inhibitors: a patent review (2021-present).

IF 5.4 2区 医学 Q1 CHEMISTRY, MEDICINAL
Fang Wang, Zhe Yang, Yujie Wu, Huanrong Bai, Minhang Xin
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引用次数: 0

Abstract

Introduction: Acute leukemia harboring rearrangement of the Mixed lineage leukemia (MLL) and/or mutation of the nucleophosmin is a type of poorly prognostic and highly malignant leukemia which is extremely difficult to treat. Blocking the protein-protein interaction between Menin and MLL is a strategic approach for treating leukemias, as a new direction for drug discovery. Many biotech and pharmaceutical companies made great efforts to this drug development field, and a large number of small molecular Menin-MLL PPI inhibitors were reported during the recent three years.

Areas covered: This review is to mainly summarize the Menin-MLL PPI inhibitors reported in the recent three years' patents.

Expert opinion: Although the past 12 years have witnessed the progress of the Menin-MLL PPI inhibitors in the treatment of acute leukemia, especially for leukemia harboring rearranged KMT2A and/or mutated NPM1, recent studies showed Menin-MLL PPI inhibitors suffered from new issues such as toxicity, acquired resistance, and homogenization. Therefore, new drug discovery strategies should be considered in advance. The expert opinion was proposed from several aspects, such as developing diverse chemical structures, discovering covalent inhibitors, designing small molecular PROTACs, and targeting the amino acids mutations for next-generation inhibitors.

Menin-mll 蛋白-蛋白相互作用抑制剂:专利回顾(2021 年至今)。
简介混合系白血病重排和/或核糖蛋白突变的急性白血病是一种预后不良的高度恶性白血病,极难治疗。阻断 Menin 与 MLL 之间的蛋白相互作用是治疗 AL 的战略方法,也是药物研发的新方向。许多生物技术和制药公司在这一药物开发领域做出了巨大努力,近三年来报道了大量小分子 Menin-MLL PPI 抑制剂:本综述主要总结了近三年来报道的Menin-MLL PPI抑制剂的专利情况:尽管在过去的12年中,Menin-MLL PPI抑制剂在治疗急性白血病,尤其是治疗KMT2A重排和/或NPM1突变的白血病方面取得了进展,但最近的研究表明,Menin-MLL PPI抑制剂存在毒性、获得性耐药和同质化等新问题。因此,应提前考虑新药研发策略。专家们从开发多样化的化学结构、发现共价抑制剂、设计小分子 PROTACs、针对氨基酸突变开发下一代抑制剂等几个方面提出了自己的意见。
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
CiteScore
12.10
自引率
1.50%
发文量
50
审稿时长
6-12 weeks
期刊介绍: Expert Opinion on Therapeutic Patents (ISSN 1354-3776 [print], 1744-7674 [electronic]) is a MEDLINE-indexed, peer-reviewed, international journal publishing review articles on recent pharmaceutical patent claims, providing expert opinion the scope for future development, in the context of the scientific literature. The Editors welcome: Reviews covering recent patent claims on compounds or applications with therapeutic potential, including biotherapeutics and small-molecule agents with specific molecular targets; and patenting trends in a particular therapeutic area Patent Evaluations examining the aims and chemical and biological claims of individual patents Perspectives on issues relating to intellectual property The audience consists of scientists, managers and decision-makers in the pharmaceutical industry and others closely involved in R&D Sample our Bioscience journals, sign in here to start your access, Latest two full volumes FREE to you for 14 days.
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