Back to Search Start Over

Antibody drug conjugates of cleavable amino-benzoyl-maytansinoids

Authors :
Carlos Hickey
Frank Delfino
Elizabeth Navarro
Thomas Nittoli
Shu Mao
Zhaoyuan Chen
Marcus Kelly
Arthur Kunz
Serena Carosso
Jessica R. Kirshner
Jing Shan
William C. Olson
Gavin Thurston
Markotan Thomas P
Nicholas J. Papadopoulos
Feng Zhao
Sosina Makonnen
Jan Spink
Source :
Bioorganicmedicinal chemistry. 28(23)
Publication Year :
2020

Abstract

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.

Details

ISSN :
14643391
Volume :
28
Issue :
23
Database :
OpenAIRE
Journal :
Bioorganicmedicinal chemistry
Accession number :
edsair.doi.dedup.....2d26b6d261eaed175a9a857484e41fc9