2. Academic Validation
  3. Pt(IV)-PROTAC Complexes with Synergistic Antitumor Activity and Enhanced Membrane Permeability

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

  • J Med Chem. 2025 Apr 24;68(8):8208-8225. doi: 10.1021/acs.jmedchem.4c02909.
Cheng-Xin Li 1 2,  Zhi-Ru Zou 1 2,  Shan Xu 1 2,  Jia-Hui Shi 1 2,  Yong Zou 1 2,  Ming Yan 1 2,  Xue-Jing Zhang 1 2
Affiliations

Affiliations

  • 1 State Key Laboratory of Anti-Infective Drug Discovery and Development, Sun Yat-sen University, Guangzhou 510006, China.
  • 2 Guangdong Provincial Key Laboratory of Chiral Molecules and Drug Discovery, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, China.
PMID: 40184539 DOI: 10.1021/acs.jmedchem.4c02909
Abstract

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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