A Platinum(IV) Prodrug-Perfluoroaryl Macrocyclic Peptide Conjugate Enhances Platinum Uptake in the Brain.,Journal of Medicinal Chemistry

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A Platinum(IV) Prodrug-Perfluoroaryl Macrocyclic Peptide Conjugate Enhances Platinum Uptake in the Brain.
Journal of Medicinal Chemistry ( IF 6.8 ) Pub Date : 2020-05-15 , 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}

Affiliation

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.

中文翻译：

铂（IV）前药-全氟芳基大环肽缀合物可增强大脑对铂的摄取。

有效递送至大脑限制了新型胶质母细胞瘤疗法的发展。在这里，我们介绍了顺铂的铂（IV）前药与全氟芳基肽大环化合物之间的缀合，以增加大脑的摄取。我们证明了一种这样的结合物显示出抗神经胶质瘤干样细胞的功效。我们研究了这种缀合物在小鼠中的药代动力学，并显示在用缀合物治疗后5 h，大脑中铂的量比用顺铂高15倍。

更新日期：2020-07-09

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