Antibody drug conjugates of cleavable amino-benzoyl-maytansinoids

被引：3

作者：

Nittoli, Thomas ^{[1
]}

Delfino, Frank ^{[1
]}

Kelly, Marcus ^{[1
]}

Carosso, Serena ^{[2
]}

Markotan, Thomas ^{[2
]}

Kunz, Arthur ^{[1
]}

Chen, Zhaoyuan ^{[1
]}

Mao, Shu ^{[1
]}

Shan, Jing ^{[1
]}

Navarro, Elizabeth ^{[1
]}

Zhao, Feng ^{[1
]}

Makonnen, Sosina ^{[1
]}

Hickey, Carlos ^{[1
]}

Spink, Jan ^{[2
]}

Olson, William ^{[1
]}

Kirshner, Jessica R. ^{[1
]}

Thurston, Gavin ^{[1
]}

Papadopoulos, Nicholas ^{[1
]}

机构：

[1] Regeneron Pharmaceut Inc, 777 Old Saw Mill River Rd, Tarrytown, NY 10591 USA

[2] Abzena, 360 George Patterson Blvd, Bristol, PA 19007 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY | 2020年 / 28卷 / 23期

关键词：

Antibody; Antibody drug conjugate; Maytansinoid; MUC16; DOXORUBICIN; LINKERS; ANTIGEN; POTENT;

D O I：

10.1016/j.bmc.2020.115785

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

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.

引用

页数：5

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