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近年来靶向溶质载体转运蛋白的配体和化学探针的研究进展。

Recent developments in ligands and chemical probes targeting solute carrier transporters.

机构信息

CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, 1090 Vienna, Austria.

CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, 1090 Vienna, Austria; Solgate GmbH, 3400 Klosterneuburg, Austria.

出版信息

Curr Opin Chem Biol. 2021 Jun;62:53-63. doi: 10.1016/j.cbpa.2021.01.012. Epub 2021 Mar 6.

DOI:10.1016/j.cbpa.2021.01.012
PMID:33689964
Abstract

Solute carrier (SLC) membrane transporters remain a largely unexploited target class, despite their central roles in cell identity and metabolism. This gap is reflected in the lack of high-quality chemical ligands or probes and in the small number of compounds that have progressed toward clinical development. In this review, we discuss recent advancements in SLC ligand discovery as well as new candidates that have been added to the investigational toolkit, with a particular focus on first-in-class ligands and the cognate discovery strategies. The availability of new probes expands the opportunity to elucidate the functions of SLCs and their relevance in physiology and explores any future potential of SLC druggability.

摘要

溶质载体 (SLC) 膜转运蛋白在细胞特性和代谢中起着核心作用,但它们仍然是一个尚未充分开发的靶点类别。这种差距反映在缺乏高质量的化学配体或探针,以及很少有化合物能够进入临床开发阶段。在这篇综述中,我们讨论了 SLC 配体发现的最新进展,以及新加入研究工具包的候选物,特别关注了首创类配体及其同源发现策略。新探针的出现为阐明 SLC 的功能及其在生理学中的相关性提供了更多机会,并探索了 SLC 成药性的任何未来潜力。

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