A Platinum(IV) Prodrug—Perfluoroaryl Macrocyclic Peptide Conjugate Enhances Platinum Uptake in the Brain
J. Med. Chem. 2020, 63, 13, 6741–6747
Publication Date:May 15, 2020
Colin M. FadzenColin M. Fadzen, Justin M. Wolfe, Wen Zhou, Choi-Fong Cho, Niklas von Spreckelsen, Kathryn T. Hutchinson, Yen-Chun Lee, E. Antonio Chiocca, Sean E. Lawler, Omer H. Yilmaz, Stephen J. Lippard*, and Bradley L. Pentelute
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.