Modular Assembled Targeting Chimera Enables Multimodal Targeted Protein Degradation.

ABSTRACT: Targeted protein degradation (TPD) has emerged as a promising therapeutic strategy, with advantages over traditional protein inhibition. Despite significant advancements in novel degraders such as bivalents and multitargeting proteolysis-targeting chimeras (PROTACs), key challenges persist in the development pipeline, particularly regarding the identification of highly potent degraders and the optimization of their drug-like properties. Here, we reported a multimodal modular assembled targeting chimera (multi-MOATAC) strategy that enabled intracellular click chemistry-mediated in situ assembly of ligand modules with targets, integrating multiple functional units into binary/ternary complexes. This strategy validated significantly enhanced degradation efficiency via trivalent self-as

SUBMITTER: Zhu W 

PROVIDER: S-EPMC12648310 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature