Peptidomimetics and metalloprotease inhibitors as anticancer drugs

作     者：SU Li XU WenFang 

作者机构：School of Pharmaceutical SciencesShandong UniversityJinan 250012China 

出 版 物：《Science China Chemistry》 (中国科学（化学英文版）)

年 卷 期：2009年第52卷第5期

页      面：535-548页

核心收录：

学科分类：1007[医学-药学(可授医学、理学学位)] 10[医学] 

基　　金：Supported by the National High Technology Research and Development Program of China (863 Project) (Grant No. 2007AA02Z314) the National Natural Science Foundation of China (Grant Nos. 90713041 & 30772654) the Doctoral Fund of Ministry of Education of China (Grant No. 20060422029) 

主　　题：peptidomimetics drug design metalloproteinase inhibitors anticancer agents 

摘      要：Peptidomimetics with three types, as the structural or functional mimetics of natural active peptides, can preserve the bioactivity and improve the bioavailability and the specificity towards the targets of the lead peptides. Peptidomimetics of high bioactivity can be designed through various ways including conformation restriction, modification and non-peptide design. Recently the concentration on the de-velopment of cancer chemotherapeutic drugs was transferred from cytotoxic drugs to target-based drugs, and many proteases and peptidases that play key roles in the process of tumor genesis and development was discovered, which means that peptidomimetics as potential cancer chemotherapeu-tic drugs should be paid close attention to. Our laboratory has focused on the development of small-molecule peptidomimetic inhibitors of APN, MMPs and HDACs as target-based anticancer agents. These three zinc-dependent metalloproteinases play very important roles in the process of tumor genesis, invasion, metastasis, angiogenesis and matrix degradation, so small-molecule peptidomimetic inhibitors based on them would be quite potential in the development of chemotherapeutic drugs with high selectivity.