Antibody Conjugates of 7-Ethyl-10-hydroxycamptothecin (SN-38) for Targeted Cancer Chemotherapy

被引：112

作者：

Moon, Sung-Ju ^{[1
]}

Govindan, Serengulam V. ^{[1
]}

Cardillo, Thomas M. ^{[1
]}

D'Souza, Christopher A. ^{[1
]}

Hansen, Hans J. ^{[1
]}

Goldenberg, David M. ^{[2
]}

机构：

[1] Immunomed Inc, Morris Plains, NJ 07950 USA

[2] Ctr Mol Med & Immunol, Garden State Canc Ctr, Belleville, NJ 07109 USA

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 2008年 / 51卷 / 21期

关键词：

D O I：

10.1021/jm800719t

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

CPT-11 is a clinically used cancer drug, and it is a prodrug of the potent topoisomerase I inhibitor, SN-38 (7-ethyl-10-hydroxycamptothecin). To bypass the need for the in vivo conversion of CPT-11 and increase the therapeutic index, bifunctional derivatives of SN-38 were prepared for use in anti body-based targeted therapy of cancer. The general synthetic scheme incorporated an acetylene-azide click cycloaddition step in the design, a short polyethylene glycol spacer for aqueous solubility, and a maleimide group conjugation. Conjugates of a humanized anti-CEACAM5 monoclonal antibody, hMN-14, prepared using, these SN-38 derivatives were evaluated in vitro for stability in buffer and human serum and for antigen-binding and cytotoxicity in a human colon adenocarcinoma cell line. Conjugates of hMN-14 and SN-38 derivatives 16 and 17 were found promising for further development.

引用

页码：6916 / 6926

页数：11

共 36 条

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