A novel pathway for maytansinoid release from thioether linked antibody–drug conjugates (ADCs) under oxidative conditions

Literature Information

Publication Date 2011-08-26
DOI 10.1039/C1CC14164C
Impact Factor 6.222
Authors

Nathan Fishkin, Erin K. Maloney, Ravi V. J. Chari, Rajeeva Singh


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Abstract

A novel pathway for ex vivo maytansinoid release from thioether linked antibody maytansinoid conjugates (AMCs) upon incubation in human plasma has been identified. A thioether succinimide-linked AMC can undergo chemical oxidation followed by sulfoxide elimination under mild aqueous conditions (pH 5.5–7.5, 37 °C). Oxidized thioether-linked AMCs exhibit high, target-specific cytotoxicity toward cancer cells.

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