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Review Article

药物化学研究进展及抗癌PROTACs分子的治疗潜力

卷 30, 期 14, 2023

发表于: 04 November, 2022

页: [1576 - 1622] 页: 47

弟呕挨: 10.2174/0929867329666220803112409

价格: $65

摘要

背景：PROTACs 是一种新兴技术，通过靶向蛋白质降解来解决引起疾病的蛋白质。 PROTACs 分子是双功能小分子，可同时结合感兴趣的蛋白质 (POI) 和 E3 连接酶，然后通过蛋白酶体泛素化和降解感兴趣的蛋白质。 目的：PROTACs 技术与经典抑制相比具有许多优势，例如 PROTACs 分子可以靶向细胞内蛋白质，无论其功能如何，并且具有良好的组织分布。它们能够靶向突变和过表达的蛋白质，因此可以设计出具有高降解选择性的有效分子。此外，PROTACs 分子可以靶向几乎占人类蛋白质 85% 的不可药物化蛋白质组。几种基于 PROTAC 的化合物表现出很高的治疗效力，其中一些目前正在进行临床试验。 方法：当前文章全面概述了基于 PROTAC 的抗癌化合物的当前发展以及已报道分子的构效关系。 结果：基于 PROTACs 的化合物的开发和相关药物化学研究是最活跃和最热门的研究课题之一。结论：相信当前的综述文章有助于理解更有效、毒性更小、选择性更高的基于 PROTAC 的分子的逻辑设计。

关键词: 靶向蛋白质降解，PROTACs，泛素化，降解，结构活性关系，药物化学

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