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Discovery of highly potent and selective 7-ethyl-10-hydroxycamptothecin-glucose conjugates as potential anti-colorectal cancer agents

Affiliation
State Key Laboratory of Biotherapy and Cancer Center ,West China Hospital ,Sichuan University and Collaborative Innovation Center of Biotherapy ,Chengdu ,Sichuan ,China
Yang, Chao;
Affiliation
State Key Laboratory of Biotherapy and Cancer Center ,West China Hospital ,Sichuan University and Collaborative Innovation Center of Biotherapy ,Chengdu ,Sichuan ,China
Xia, An-Jie;
Affiliation
Department of Biological Sciences ,USC Dana and David Dornsife College of Letters, Arts and Sciences ,Los Angeles ,CA ,United States
Du, Cheng-Hao;
Affiliation
State Key Laboratory of Biotherapy and Cancer Center ,West China Hospital ,Sichuan University and Collaborative Innovation Center of Biotherapy ,Chengdu ,Sichuan ,China
Hu, Ming-Xing;
Affiliation
Department of Thoracic Oncology ,West China Hospital ,Sichuan University ,Chengdu ,Sichuan ,China
Gong, You-Ling;
Affiliation
Department of Nuclear Medicine ,West China Hospital ,Sichuan University ,Chengdu ,Sichuan ,China
Tian, Rong;
Affiliation
Department of Pediatric Surgery ,West China Hospital ,Sichuan University ,Chengdu ,Sichuan ,China
Jiang, Xin;
Affiliation
State Key Laboratory of Biotherapy and Cancer Center ,West China Hospital ,Sichuan University and Collaborative Innovation Center of Biotherapy ,Chengdu ,Sichuan ,China
Xie, Yong-Mei

7-Ethyl-10-hydroxycamptothecin (SN38), a highly potent metabolite of irinotecan, has an anticancer efficacy 100–1000 folds more than irinotecan in vitro . However, the clinical application of SN38 has been limited due to the very narrow therapeutic window and poor water solubility. Herein, we report the SN38-glucose conjugates (Glu-SN38) that can target cancer cells due to their selective uptake via glucose transporters, which are overexpressed in most cancers. The in vitro antiproliferative activities against human cancer cell lines and normal cells of Glu-SN38 were investigated. One of the conjugates named 5b showed high potency and selectivity against human colorectal cancer cell line HCT116. Furthermore, 5b remarkably inhibited the growth of HCT116 in vivo . These results suggested that 5b could be a promising drug candidate for treating colorectal cancer.

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License Holder: Copyright © 2022 Yang, Xia, Du, Hu, Gong, Tian, Jiang and Xie.

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