UBE2N: Hope on the Cancer Front, How to Inhibit This Promising Target Prospect?

IF 6.8 1区医学 Q1 CHEMISTRY, MEDICINAL

Journal of Medicinal Chemistry Pub Date : 2025-01-13 DOI:10.1021/acs.jmedchem.4c01517

Florian Schwalen, Côme Ghadi, Léonie Ibazizene, Shafi Ullah Khan, Jana Sopkova-de Oliveira Santos, Louis-Bastien Weiswald, Anne Sophie Voisin-Chiret, Matthieu Meryet-Figuiere, Charline Kieffer

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Abstract

UBE2N protein belongs to the UE2s family and plays a crucial role in DNA repair, making it an exciting target for the development of innovative anticancer therapies. With the aim of discovering UBE2N inhibitors (UBE2Ni), this perspective seeks to review and provide elements to guide the design of new compounds. We propose a chemoinformatic structural analysis of the protein and its areas of interaction with its different partners. While covalent UBE2Ni are the most advanced molecules in their development, noncovalent inhibitors offer significant advantages that could overcome the limitations of covalent ones, particularly in terms of selectivity. Lastly, to obtain a drug candidate, early assessment of the druggability of compounds is essential in a hit to lead process. For existing UBE2Ni, a critical challenge lies in their pharmacokinetic properties and will obviously have to be considered as early as possible to hope for an application in human therapy.

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UBE2N：癌症前沿的希望，如何抑制这一有希望的靶标前景？

UBE2N 蛋白属于 UE2s 家族，在 DNA 修复中起着至关重要的作用，因此成为开发创新抗癌疗法的一个令人兴奋的靶点。为了发现 UBE2N 抑制剂（UBE2Ni），本研究试图回顾并提供指导新化合物设计的要素。我们建议对该蛋白质及其与不同伙伴的相互作用领域进行化学信息学结构分析。虽然共价 UBE2Ni 是目前最先进的分子，但非共价抑制剂也具有显著优势，可以克服共价抑制剂的局限性，尤其是在选择性方面。最后，要获得候选药物，在 "从一击到先导 "的过程中，早期评估化合物的可药性至关重要。对于现有的 UBE2Ni，关键的挑战在于它们的药代动力学特性，显然必须尽早考虑将其应用于人体治疗。

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 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.