铂（IV）前药-全氟芳基大环肽缀合物增强脑内铂的摄取。
A Platinum(IV) Prodrug-Perfluoroaryl Macrocyclic Peptide Conjugate Enhances Platinum Uptake in the Brain.
机构信息
Department of Chemistry, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, United States.
The Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, United States.
出版信息
J Med Chem. 2020 Jul 9;63(13):6741-6747. doi: 10.1021/acs.jmedchem.0c00022. Epub 2020 Jun 26.
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.
摘要
有效递送到大脑限制了新型胶质母细胞瘤疗法的发展。在这里，我们介绍顺铂的铂（IV）前药与全氟芳基肽大环的连接，以增加脑摄取。我们证明了这样的一种缀合物对神经胶质瘤干细胞具有疗效。我们研究了这种缀合物在小鼠中的药代动力学，结果表明，在用缀合物治疗 5 小时后，大脑中的铂含量是顺铂的 15 倍。
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2
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3
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Cancer Lett. 2018 Mar 1;416:138-148. doi: 10.1016/j.canlet.2017.11.041. Epub 2017 Dec 13.
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5
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6
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8
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9
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