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. 2025 Nov 25;61(95):18902-18905.
doi: 10.1039/d5cc05824d.

Towards a glutathione-cleavable azobenzene linker for antibody-drug conjugates

Mia Kapun  1 , Roshan Patel  1 , Mahri Park  1 , F Javier Pérez-Areales  1 , Kristina A Kostadinova  1 , Thomas Wharton  1 , Jason S Carroll  2 , David R Spring  1
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Towards a glutathione-cleavable azobenzene linker for antibody-drug conjugates

Mia Kapun et al. Chem Commun (Camb). .

Abstract

Herein we describe the development of a novel azobenzene-containing glutathione-cleavable linker for use in antibody-drug conjugates (ADCs). This linker demonstrated efficient payload release under elevated glutathione levels while maintaining stability in human plasma. An anti-HER2 ADC incorporating this linker exhibited potent in vitro cytotoxicity and selective activity towards HER2-positive cell lines.

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