文献类型：期刊文献

英文题名：Exploiting Protein Phosphatase Inhibitors Based on Cantharidin Analogues for Cancer Drug Discovery

作者：Deng, Liping[1];Dong, Jian[1];Wang, Wei[2]

机构：[1]Shaoxing Univ, Dept Pharmacol, Chem & Chem Engn Inst, Shaoxing 312000, Zhejiang, Peoples R China;[2]Zhejiang Supor Pharmaceut, Shaoxing 312000, Zhejiang, Peoples R China

年份：2013

卷号：13

期号：8

起止页码：1166

外文期刊名：MINI-REVIEWS IN MEDICINAL CHEMISTRY

收录：SCI-EXPANDED(收录号：WOS:000318973800005)、、Scopus(收录号：2-s2.0-84881525886)、WOS

基金：This project is funded by the Natural Science Foundation of Zhejiang Province, China (Y2100872 and LY12E03001). The authors also acknowledge the financial support of the National Natural Science Foundation of China (81202411 and 20974063).

语种：英文

外文关键词：Cantharidin; antitumor; norcantharidin; PP1; PP2A; structure-activity relationship

外文摘要：Cantharidin (CTD), a natural toxin, can inhibit a variety of tumor cell lines, especially hepatocellular carcinoma cells. It is a strong inhibitor of protein phosphatase type 1 (PP1) and type 2A (PP2A). Because of the cytotoxicity, the clinical application of CDT is limited. Here, we review the structure-activity relationships of CDT analogues, including norcantharidin (NCTD), cantharimides and related derivatives of CTDs, which have more powerful antitumor activity but less cytotoxicity than CDT itself. Important advances in the design of the CTD-based inhibitors achieved recently are outlined here in order to establish principles for synthesis, screening, and the applications of promising anti-cancer drug candidates. In addition, efforts to ameliorate the intrinsic cytotoxicity through the use of drug carriers are also discussed. It is conceivable that rational design of the protein phosphatase inhibitors based on cantharidin analogues can be facilitated by studies of mechanism of the protein-inhibitor interactions and the related structural biology in the future.