A Platinum(IV) Prodrug—Perfluoroaryl Macrocyclic Peptide Conjugate Enhances Platinum Uptake in the Brain
Name
nihms-1679329.pdf
Description
Accepted version
Size
825.68 KB
Format
Adobe PDF
Checksum (MD5)
52892cbe86d47254716a65cbe576a747
Author(s)
Fadzen, Colin M
Wolfe, Justin M
Zhou, Wen
Cho, Choi-Fong
von Spreckelsen, Niklas
Hutchinson, Kathryn T
Lee, Yen-Chun
Chiocca, E Antonio
Lawler, Sean E
Yilmaz, Omer H
Date Issued
2020
Journal
Journal of Medicinal Chemistry
Publisher
American Chemical Society (ACS)
Version
Author's final manuscript
Abstract
© 2020 American Chemical Society. 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.
MIT Department
Massachusetts Institute of Technology. Department of Chemistry
Koch Institute for Integrative Cancer Research at MIT
Terms of Use
Creative Commons Attribution-Noncommercial-Share Alike
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DOI of Published Version
https://doi.org/10.1021/ACS.JMEDCHEM.0C00022
