基于金属的抗癌药物由于其特定的配位几何结构和反应性而占据了不同的化学空间。尽管最初的DNA靶向典范适用于这类化合物，但现在清楚地认识到它们也可以根据金属和配体支架调节以针对细胞内的蛋白质。由于金属药物的发现主要基于表型筛选，因此量身定制的蛋白质组学策略对于确定和验证多种研究和临床先进的基于金属药物的蛋白质靶点至关重要。在这里，我们讨论了这样的实验方法，这些方法表明基于钌、金、铼甚至铂的金属药物可以选择性地和特异性地靶向蛋白质，并产生明显的下游效应。预计靶标鉴定策略将大力支持机制驱动的基于金属药物的临床转化。 版权所有 © 2022 作者。由 Elsevier Ltd. 发布。保留所有权利。

Metal-based anticancer agents occupy a distinct chemical space due to their particular coordination geometry and reactivity. Despite the initial DNA-targeting paradigm for this class of compounds, it is now clear that they can also be tuned to target proteins in cells, depending on the metal and ligand scaffold. Since metallodrug discovery is dominated by phenotypic screenings, tailored proteomics strategies were crucial to identify and validate protein targets of several investigative and clinically advanced metal-based drugs. Here, such experimental approaches are discussed, which showed that metallodrugs based on ruthenium, gold, rhenium and even platinum, can selectively and specifically target proteins with clear-cut down-stream effects. Target identification strategies are expected to support significantly the mechanism-driven clinical translation of metal-based drugs.Copyright © 2022 The Author(s). Published by Elsevier Ltd.. All rights reserved.