Sculpting Cell Fate: The Expanding Universe of Nondegradative Proximity‐Inducing Tools

作者：Hangdi Xiao, Lan Wang, Mengxiao Chen, Tengfei Zhen, Yao Chen, Haopeng Sun · 发表于：ChemMedChem · 年份：2026 · DOI：10.1002/cmdc.202501088 · 被引用次数：1 · 研究领域：Protein Degradation and Inhibitors、Click Chemistry and Applications、Chromatin Remodeling and Cancer

The paradigm of targeted therapy has been revolutionized by the development of proximity-inducing chimeras, particularly proteolysis-targeting chimeras (PROTACs), which offer a therapeutic strategy for previously "undruggable" targets. However, the degradation of certain essential proteins can lead to off-target toxicity, prompting the development of nondegradative proximity-inducing chimeras. This review categorizes current nondegradative chimeras into several functional classes, including targeted inhibition, targeted stabilization, post-translational modification (PTM), and cellular switches; elaborates on the mechanisms of action for each category; and introduces representative technologies, including molecular glues (MGs). Furthermore, the review highlights cutting-edge research and recent advancements in the field. Unlike previous reviews focusing primarily on degradative chimera technologies, this article systematically categorizes nondegradative modalities into inhibition, stabilization, PTM, and cellular switches, providing a unified mechanistic framework and highlighting emerging therapeutic applications beyond oncology.