Monomeric Targeted Protein Degraders

作者：Emily J. Hanan, Jun Liang, Xiaojing Wang, Robert A. Blake, Nicole Blaquière, Steven T. Staben · 发表于：Journal of Medicinal Chemistry · 年份：2020 · DOI：10.1021/acs.jmedchem.0c00093 · 被引用次数：63 · 研究领域：Protein Degradation and Inhibitors、Ubiquitin and proteasome pathways、Peptidase Inhibition and Analysis

The discovery and development of targeted protein degraders have become important areas of research in the field of medicinal chemistry. Inducing degradation of a target protein presents several advantages relative to simple inhibition including a potential for extended duration of action and more profound pharmacology. While engineered heterodimeric molecules have recently been a major focus within industry and academia, this Perspective highlights examples of targeted protein degradation observed for smaller, monomeric molecules. Methods and tools for evaluating protein degradation as well as a discussion of physical properties of monomeric vs engineered heterodimeric degraders are presented.