Cellular, Structural Basis, and Recent Progress for Targeting Murine Double Minute X (MDMX) in Tumors.

IF 6.8 1区 医学 Q1 CHEMISTRY, MEDICINAL
Journal of Medicinal Chemistry Pub Date : 2024-09-12 Epub Date: 2024-08-26 DOI:10.1021/acs.jmedchem.4c00913
Qikun Yin, Yuemiao Hu, Zhiwen Dong, Jing Lu, Hongbo Wang
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引用次数: 0

Abstract

Murine double minute X (MDMX) is an oncoprotein that mainly has a negative regulatory effect on the tumor suppressor p53 to induce tumorigenesis. As MDMX is highly expressed in various types of tumor cells, targeting and inhibiting MDMX are becoming a promising strategy for treating cancers. However, the high degree of structural homology between MDMX and its homologous protein murine double minute 2 (MDM2) is a great challenge for the development of MDMX-targeted therapies. This review introduces the structure, distribution, and regulation of the MDMX, summarizes the structural features and structure-activity relationships (SARs) of MDMX ligands, and focuses on the differences between MDMX and MDM2 in these aspects. Our purpose of this work is to propose potential strategies to achieve the specific targeting of MDMX.

Abstract Image

靶向肿瘤中的小鼠双敏 X (MDMX) 的细胞、结构基础和最新进展。
鼠双分 X(MDMX)是一种肿瘤蛋白,主要对肿瘤抑制因子 p53 起负性调控作用,诱导肿瘤发生。由于 MDMX 在各类肿瘤细胞中高表达,因此靶向抑制 MDMX 正成为治疗癌症的一种前景广阔的策略。然而,MDMX与其同源蛋白鼠双分蛋白2(MDM2)在结构上的高度同源性是开发MDMX靶向疗法的巨大挑战。本综述介绍了MDMX的结构、分布和调控,总结了MDMX配体的结构特征和结构-活性关系(SARs),并重点讨论了MDMX和MDM2在这些方面的差异。我们这项工作的目的是提出实现特异性靶向 MDMX 的潜在策略。
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
Journal of Medicinal Chemistry
Journal of Medicinal Chemistry 医学-医药化学
CiteScore
4.00
自引率
11.00%
发文量
804
审稿时长
1.9 months
期刊介绍: The Journal of Medicinal Chemistry is a prestigious biweekly peer-reviewed publication that focuses on the multifaceted field of medicinal chemistry. Since its inception in 1959 as the Journal of Medicinal and Pharmaceutical Chemistry, it has evolved to become a cornerstone in the dissemination of research findings related to the design, synthesis, and development of therapeutic agents. The Journal of Medicinal Chemistry is recognized for its significant impact in the scientific community, as evidenced by its 2022 impact factor of 7.3. This metric reflects the journal's influence and the importance of its content in shaping the future of drug discovery and development. The journal serves as a vital resource for chemists, pharmacologists, and other researchers interested in the molecular mechanisms of drug action and the optimization of therapeutic compounds.
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