药学学报, 2021, 56(2): 403-413
引用本文:
段雨婷, 蒙凌华. 多靶点抗肿瘤天然产物研究进展[J]. 药学学报, 2021, 56(2): 403-413.
DUAN Yu-ting, MENG Ling-hua. Research progress in multi-targeted anti-tumor natural products[J]. Acta Pharmaceutica Sinica, 2021, 56(2): 403-413.

多靶点抗肿瘤天然产物研究进展
段雨婷1,2, 蒙凌华1,2
1. 中国科学院上海药物研究所, 上海 201203;
2. 中国科学院大学, 北京 100049
摘要:
天然产物及其衍生物是抗肿瘤药物的重要组成部分。目前在临床上应用的天然产物来源的抗肿瘤药物以传统细胞毒类药物或靶向某一特定靶点的分子靶向药物为主,其应用受限于药物相关不良反应和肿瘤耐药。近年的研究表明,抗肿瘤活性天然产物往往能够靶向肿瘤细胞的多个靶点,影响肿瘤发生发展中的多个过程。由于肿瘤是一种多因素诱发的系统性疾病,多靶点天然产物在肿瘤治疗方面具有独特潜力。目前已发现的多靶点抗肿瘤天然产物的作用靶标和作用机制往往不够明确,限制了其进一步的开发。本文基于现代分子药理学理论,以多个典型的多靶点抗肿瘤天然产物为例进行综述,介绍了目前这些多靶点药物的作用机制、靶点确认和结构优化等研究进展,并对其作为抗肿瘤药物的研发前景进行了展望。
关键词:    多靶点      抗肿瘤药物      天然产物      靶点确证      结构优化     
Research progress in multi-targeted anti-tumor natural products
DUAN Yu-ting1,2, MENG Ling-hua1,2
1. Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China;
2. University of Chinese Academy of Sciences, Beijing 100049, China
Abstract:
Natural products and their derivatives are important components of anti-tumor drugs. Currently, anti-tumor drugs derived from natural products which are in clinical practice are mainly conventional cytotoxic or molecularly targeted drugs. Their application is limited by drug-related side effects and drug resistance. Recent studies have shown that anti-tumor natural products often act on multiple targets in tumor cells and in turn interfere with multiple processes in tumorigenesis and development. As tumor is a systemic disease induced by multiple factors, multi-targeted natural products possess unique potential in tumor therapy. However, the targets and mechanisms of the discovered multi-targeted antitumor natural products remain elusive, which limits their further development and application. This review summarized the research progress in the mechanism of action, target identification, and structure optimization of multi-targeted anti-tumor natural products exemplified by a few typical compounds. The research and development of these agents have also been proposed.
Key words:    multi-targeted    anti-tumor drug    natural product    target validation    structure optimization   
收稿日期: 2020-07-22
DOI: 10.16438/j.0513-4870.2020-1224
基金项目: 国家自然科学基金资助项目(81773760).
通讯作者: 蒙凌华,Tel:86-21-50801669,E-mail:lhmeng@simm.ac.cn
Email: lhmeng@simm.ac.cn
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