Antibody Drug Conjugates Of Cleavable Amino-Benzoyl-Maytansinoids

BIOORGANIC & MEDICINAL CHEMISTRY(2020)

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摘要
ADCs based on the natural product maytansine have been successfully employed clinically. In a previous report, ADCs based on hydrophilic non-cell permeable maytansinoids was presented. The authors in this report further explore the maytansine scaffold to develop tubulin inhibitors capable of cell permeation. The research resulted in amino-benzoyl-maytansinoid payloads that were further elaborated with linkers for conjugating to antibodies. This approach was applied to MUC16 tumor targeting antibodies for ovarian cancers. A positive control ADC was evaluated alongside the amino-benzoyl-maytansinoid ADC and the efficacy observed was equivalent while the isotype control ADCs had no effect.
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关键词
Antibody, Antibody drug conjugate, Maytansinoid, MUC16
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