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Updated: May 19, 2026

Amide Coupling Reaction for the Synthesis of Bispyridine-based Ligands and Their Complexation to Platinum as Dinuclear Anticancer Agents
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Published on: May 28, 2014

Radiotherapy Activates Drug-Drug Conjugates for Platinum-Based Combinational Chemotherapy.

Siyong Shen1, Qunfeng Fu1, Yuchen Hu1

  • 1Beijing National Laboratory for Molecular Sciences, Cross-disciplinary Center for f-Elements (CCFE), Radiochemistry and Radiation Chemistry Key Laboratory of Fundamental Science, Key Laboratory of Bioorganic Chemistry and Molecular Engineering of Ministry of Education, College of Chemistry and Molecular Engineering, Peking University, Beijing 100871, China.

Journal of Medicinal Chemistry
|May 18, 2026
PubMed
Summary
This summary is machine-generated.

This study introduces a novel platinum(IV) prodrug activated by radiotherapy, enhancing cancer treatment by reducing systemic toxicity. The platform selectively releases two agents in tumors, improving drug delivery and efficacy.

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Area of Science:

  • Oncology
  • Radiotherapy
  • Medicinal Chemistry

Background:

  • Platinum-based chemotherapy is standard for major cancers but limited by dose-limiting toxicity.
  • Concurrent chemoradiotherapy efficacy is hampered by systemic drug side effects.

Purpose of the Study:

  • To develop a radiotherapy-activated platinum(IV) prodrug platform for selective tumor activation.
  • To reduce systemic toxicity in concurrent chemoradiotherapy.
  • To enhance platinum-based combination therapy efficacy.

Main Methods:

  • Synthesized and screened a library of Pt(IV) prodrugs with varied functional groups and linkages.
  • Incorporated bioactive ligands for irradiation-triggered release of cytotoxic agents.
  • Integrated a human serum albumin (HSA)-binding motif to improve pharmacokinetics.

Main Results:

  • Identified Pt(IV) prodrugs with optimal stability and radiation-triggered reactivity.
  • Demonstrated selective activation of prodrugs within tumors upon irradiation.
  • Showcased enhanced tumor accumulation and prolonged circulation time via HSA binding.

Conclusions:

  • Established a chemical platform for radiotherapy-activated platinum(IV) prodrugs.
  • Achieved selective release of two bioactive agents in tumors, enhancing combination therapy.
  • Improved pharmacokinetic profiles and antitumor efficacy through albumin-mediated transport and targeted drug activation.