期刊
NATURE COMMUNICATIONS
卷 11, 期 1, 页码 -出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/s41467-019-14091-4
关键词
-
资金
- Innosuisse [25174.1 PFLS-LS]
- Central Environmental Laboratory (EPFL, Lausanne, Switzerland)
- Swiss Chemical Industry (SSCI)
- Natural Sciences and Engineering Research Council of Canada (NSERC) [RGPIN-2015-05364]
Myo-inositol hexakisphosphate (IP6) is a natural product known to inhibit vascular calcification (VC), but with limited potency and low plasma exposure following bolus administration. Here we report the design of a series of inositol phosphate analogs as crystallization inhibitors, among which 4,6-di-O-(methoxy-diethyleneglycol)-myo-inositol-1,2,3,5-tetrakis(phosphate), (OEG(2))(2)-IP4, displays increased in vitro activity, as well as more favorable pharmacokinetic and safety profiles than IP6 after subcutaneous injection. (OEG(2))(2)-IP4 potently stabilizes calciprotein particle (CPP) growth, consistently demonstrates low micromolar activity in different in vitro models of VC (i.e., human serum, primary cell cultures, and tissue explants), and largely abolishes the development of VC in rodent models, while not causing toxicity related to serum calcium chelation. The data suggest a mechanism of action independent of the etiology of VC, whereby (OEG(2))(2)-IP4 disrupts the nucleation and growth of pathological calcification.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据