2. Academic Validation
  3. A Platinum(IV) Prodrug-Perfluoroaryl Macrocyclic Peptide Conjugate Enhances Platinum Uptake in the Brain

A Platinum(IV) Prodrug-Perfluoroaryl Macrocyclic Peptide Conjugate Enhances Platinum Uptake in the Brain

  • J Med Chem. 2020 Jul 9;63(13):6741-6747. doi: 10.1021/acs.jmedchem.0c00022.
Colin M Fadzen 1,  Justin M Wolfe 1,  Wen Zhou 1 2,  Choi-Fong Cho 3,  Niklas von Spreckelsen 3 4,  Kathryn T Hutchinson 3,  Yen-Chun Lee 1,  E Antonio Chiocca 3,  Sean E Lawler 3,  Omer H Yilmaz 2,  Stephen J Lippard 1,  Bradley L Pentelute 1 2
Affiliations

Affiliations

  • 1 Department of Chemistry, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, United States.
  • 2 The Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, United States.
  • 3 Harvey Cushing Neuro-Oncology Laboratories, Department of Neurosurgery, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, United States.
  • 4 Department of Neurosurgery, Center for Neurosurgery, Faculty of Medicine and University Hospital, University of Cologne 50937 Cologne, Germany.
PMID: 32410451 DOI: 10.1021/acs.jmedchem.0c00022
Abstract

Effective delivery to the brain limits the development of novel glioblastoma therapies. Here, we introduce conjugation between platinum(IV) prodrugs of cisplatin and perfluoroaryl peptide macrocycles to increase brain uptake. We demonstrate that one such conjugate shows efficacy against glioma stem-like cells. We investigate the pharmacokinetics of this conjugate in mice and show that the amount of platinum in the brain after treatment with the conjugate is 15-fold greater than with cisplatin after 5 h.

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  • HY-P10782
    Anticancer agent