Pt(IV)-PROTAC Complexes with Synergistic Antitumor Activity and Enhanced Membrane Permeability

被引：0
|
作者：
Li, Cheng-xin [1 ,2 ]
Zou, Zhi-ru [1 ,2 ]
Xu, Shan [1 ,2 ]
Shi, Jia-hui [1 ,2 ]
Zou, Yong [1 ,2 ]
Yan, Ming [1 ,2 ]
Zhang, Xue-jing [1 ,2 ]
机构：
[1] Sun Yat Sen Univ, State Key Lab Antiinfect Drug Discovery & Dev, Guangzhou 510006, Peoples R China
[2] Sun Yat Sen Univ, Sch Pharmaceut Sci, Guangdong Prov Key Lab Chiral Mol & Drug Discovery, Guangzhou 510006, Peoples R China
来源：
JOURNAL OF MEDICINAL CHEMISTRY | 2025年
关键词：
NUCLEOTIDE EXCISION-REPAIR; ANTICANCER ACTIVITY; PLATINUM DRUGS; CANCER; DELIVERY; FLUDARABINE; INHIBITOR; PRODRUGS; PARP1;
D O I：
10.1021/acs.jmedchem.4c02909
中图分类号：
R914 [药物化学];
学科分类号：
100701 ;
摘要：
A class of Pt(IV)-PROTAC complexes was designed and synthesized with dual aims of inducing DNA strand damage and inhibiting DNA repair. These complexes showed good antiproliferative activity against a range of cancer cell lines. Enhanced intracellular uptake of platinum and PROTAC was observed. Multiple mechanisms of action were identified, including the induction of DNA damage, disruption of DNA repair, and activation of mitochondrial-dependent apoptosis. One of the Pt(IV)-PROTACs, CW-2, showed excellent antitumor activity in a xenograft mouse model. These results suggest that Pt(IV)-PROTAC represents a promising strategy for the development of novel antitumor therapeutics.
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页数：18
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