Open AccessA Platinum(IV) Prodrug—Perfluoroaryl Macrocyclic Peptide Conjugate Enhances Platinum Uptake in the Brain
Author(s) -
Colin M. Fadzen,
Justin M. Wolfe,
Wen Zhou,
Choi-Fong Cho,
Niklas von Spreckelsen,
Kathryn T. Hutchinson,
YenChun Lee,
E. Antonio Chiocca,
Sean Lawler,
Ömer H. Yılmaz,
Stephen J. Lippard,
Bradley L. Pentelute
Publication year - 2020
Publication title -
journal of medicinal chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.01
H-Index - 261
eISSN - 1520-4804
pISSN - 0022-2623
DOI - 10.1021/acs.jmedchem.0c00022
Subject(s) - conjugate , prodrug , chemistry , cisplatin , platinum , pharmacokinetics , peptide , glioma , pharmacology , combinatorial chemistry , stereochemistry , chemotherapy , biochemistry , cancer research , medicine , catalysis , mathematical analysis , mathematics
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.