Status and progress of tetravalent platinum prodrugs
10.11665/j.issn.1000-5048.20220512
- VernacularTitle:四价铂前药研究现状与进展
- Author:
Jie ZHU
1
;
Chen ZHANG
;
Jianbing WU
;
Yihua ZHANG
;
Zhangjian HUANG
Author Information
1. 中国药科大学新药研究中心
- Publication Type:Journal Article
- From:
Journal of China Pharmaceutical University
2022;53(5):613-622
- CountryChina
- Language:Chinese
-
Abstract:
Bivalent platinum drugs [Pt(II)] represented by cisplatin are the first-line drugs in clinical application, but they have defects such as severe side-effects, poor bioavailability and drug resistance.Tetravalent platinum [Pt(IV)] complexes, derivatives of Pt(II) with different substitutions in axial positions, can be reduced to Pt(II) under the action of reductants in tumor, and can therefore act as a prodrug of Pt(II).Axial substituents can improve platinum drugs'' pharmacokinetics, selectivity and bioactivity, as well as achieve anti-tumor effect by additional cytotoxic mechanisms other than DNA damage, which can overcome the drug resistance to Pt(II).This review outlines the resistance mechanisms of platinum drugs, including platinum transport, detoxification, autophagy, and DNA repair, etc.It also summarizes the structure-activity relationship, main types and advances of tetravalent platinum prodrugs, as well as possible approach to solve platinum drug resistance.
