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蛋白质-蛋白质相互作用作为抗生素靶点:药物化学视角。

Protein-protein interactions as antibiotic targets: A medicinal chemistry perspective.

机构信息

Discipline of Chemistry, School of Environmental & Life Sciences, The University of Newcastle, Callaghan, Australia.

Centre for Chemical Biology and Clinical Pharmacology, Department of Biology, School of Environmental & Life Sciences, The University of Newcastle, Callaghan.

出版信息

Med Res Rev. 2020 Mar;40(2):469-494. doi: 10.1002/med.21519. Epub 2018 Jul 13.

Abstract

There are 27 small molecule protein-protein interaction (PPI) modulators in Phase I, II, and III clinical trials targeting cancer, viruses, autoimmune disorders, and as immune suppression agents. Targeting PPIs as an antibiotic drug discovery strategy remains in relative infancy by comparison. However, a number of molecules are in development which target PPI within the replisome, divisome, transcriptome, and translatome are showing significant promise at the medicinal chemistry stage of drug development. Hence, the success of future PPI agents as antibiotics will build upon the techniques and design strategies of these molecules.

摘要

目前有 27 种小分子蛋白-蛋白相互作用(PPI)调节剂处于针对癌症、病毒、自身免疫性疾病和免疫抑制的 I 期、II 期和 III 期临床试验阶段。相比之下,将 PPI 作为抗生素药物发现策略仍处于相对初级的阶段。然而,许多分子正在开发中,它们针对复制体、分裂体、转录组和翻译组中的 PPI,在药物开发的药物化学阶段显示出了显著的前景。因此,未来 PPI 作为抗生素的成功将建立在这些分子的技术和设计策略的基础上。

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