Department of Experimental Oncology, IEO, European Institute of Oncology IRCCS, Milan, Italy.
Department of Oncology and Hematology-Oncology, University of Milan, Milan, Italy.
Proteomics. 2023 Dec;23(23-24):e2200435. doi: 10.1002/pmic.202200435. Epub 2023 Sep 19.
The combined activity of epigenetic features, which include histone post-translational modifications, DNA methylation, and nucleosome positioning, regulates gene expression independently from changes in the DNA sequence, defining how the shared genetic information of an organism is used to generate different cell phenotypes. Alterations in epigenetic processes have been linked with a multitude of diseases, including cancer, fueling interest in the discovery of drugs targeting the proteins responsible for writing, erasing, or reading histone and DNA modifications. Mass spectrometry (MS)-based proteomics has emerged as a versatile tool that can assist drug discovery pipelines from target validation, through target deconvolution, to monitoring drug efficacy in vivo. Here, we provide an overview of the contributions of MS-based proteomics to epigenetic drug discovery, describing the main approaches that can be used to support different drug discovery pipelines and highlighting how they contributed to the development and characterization of epigenetic drugs.
组蛋白翻译后修饰、DNA 甲基化和核小体定位等表观遗传特征的联合活性可独立于 DNA 序列的变化来调节基因表达，从而定义生物体共享遗传信息如何用于产生不同的细胞表型。表观遗传过程的改变与多种疾病有关，包括癌症，这激发了人们对发现针对负责书写、擦除或读取组蛋白和 DNA 修饰的蛋白质的药物的兴趣。基于质谱 (MS) 的蛋白质组学已成为一种多功能工具，可从靶标验证、靶标分解、到体内监测药物疗效等各个方面协助药物发现管道。在这里，我们概述了基于 MS 的蛋白质组学在表观遗传药物发现中的贡献，描述了可用于支持不同药物发现管道的主要方法，并强调了它们如何有助于开发和表征表观遗传药物。
