Structure‐Activity Relationships of Metal‐Based Inhibitors of the Mitochondrial Calcium Uniporter
Structure‐Activity Relationships of Metal‐Based Inhibitors of the Mitochondrial Calcium Uniporter
复制标题
线粒体钙单向转运蛋白金属抑制剂的结构与活性关系
DOI：
10.1002/cmdc.202300106
复制
发表时间：
2023
期刊：
影响因子：
3.4
通讯作者：
Wilson, Justin J.
中科院分区：
文献类型：
--
作者：
Huang, Zhouyang;Wilson, Justin J.
线粒体钙单向转运蛋白（MCU）是一种跨膜蛋白，负责介导线粒体钙（mCa2+）摄取。鉴于这一关键功能，MCU被认为是解决各种人类疾病的重要目标。因此，人们对开发可以抑制这种蛋白质的小分子越来越感兴趣。迄今为止，金属配位络合物，特别是多核钌络合物，是最广泛研究的MCU抑制剂，由于它们的有效抑制活性以及它们长期用于该应用。最近的努力已经扩展了用于MCU抑制的金属基工具包。这篇概念论文总结了MCU的新型金属基抑制剂的开发及其结构活性关系，以提高其在管理人类疾病相关tomCa2+失调中的治疗用途潜力。
The mitochondrial calcium uniporter (MCU) is a transmembrane protein that is responsible for mediating mitochondrial calcium (mCa2+) uptake. Given this critical function, the MCU has been implicated as an important target for addressing various human diseases. As such, there has a been growing interest in developing small molecules that can inhibit this protein. To date, metal coordination complexes, particularly multinuclear ruthenium complexes, are the most widely investigated MCU inhibitors due to both their potent inhibitory activities as well as their longstanding use for this application. Recent efforts have expanded the metal‐based toolkit for MCU inhibition. This concept paper summarizes the development of new metal‐based inhibitors of the MCU and their structure‐activity relationships in the context of improving their potential for therapeutic use in managing human diseases related tomCa2+dysregulation.