Inside Front Cover: Enzyme-Activated Orthogonal Proteolysis Chimeras for Tumor Microenvironment-Responsive Immunomodulation (Angew. Chem. Int. Ed. 22/2025)

Abstract

Novel tumor microenvironment-responsive enzyme-activated clickable PROTACs, termed as ENCTACs, are presented by Bengang Xing et al. in their Research Article (e202423057). Such ENCTACs enable selective formation of heterobifunctional degraders to disrupt BRD4 in tumor, effectively downregulating PD−L1 for immunotherapy. The cover illustration depicts fragments conjugation after enzyme reaction, realizing protein intervention and activating the antitumoral immune system.