Antibody drug conjugates of cleavable amino-benzoyl-maytansinoids. Issue 23 (1st December 2020)

• Record Type: Journal Article
• Authors: Nittoli, Thomas; Delfino, Frank; Kelly, Marcus; Carosso, Serena; Markotan, Thomas; Kunz, Arthur; Chen, Zhaoyuan; Mao, Shu; Shan, Jing; Navarro, Elizabeth; Zhao, Feng; Makonnen, Sosina; Hickey, Carlos; Spink, Jan; Olson, William; Kirshner, Jessica R.; Thurston, Gavin; Papadopoulos, Nicholas
• Is Part Of: Bioorganic & medicinal chemistry. Volume 28:Issue 23(2020)
• Publication Date: 2020-12-01
• Subjects: Antibody -- Antibody drug conjugate -- Maytansinoid -- MUC16; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; Biochemistry -- Periodicals; Chemistry, Clinical -- Periodicals; Chemistry, Organic -- Periodicals; Chimie bio-organique -- Périodiques; Chimie pharmaceutique -- Périodiques; 615.19
• DOI: 10.1016/j.bmc.2020.115785
• Languages: English
• ISSNs: 0968-0896

Abstract

Graphical abstract: 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.