Inhibition of vascular calcification by inositol phosphates derivatized with ethylene glycol oligomers

Open access
Date
2020Type
- Journal Article
Citations
Cited 27 times in
Web of Science
Cited 27 times in
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ETH Bibliography
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Abstract
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), (OEG2)2-IP4, displays increased in vitro activity, as well as more favorable pharmacokinetic and safety profiles than IP6 after subcutaneous injection. (OEG2)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 (OEG2)2-IP4 disrupts the nucleation and growth of pathological calcification. Show more
Permanent link
https://doi.org/10.3929/ethz-b-000399364Publication status
publishedExternal links
Journal / series
Nature CommunicationsVolume
Pages / Article No.
Publisher
Nature Publishing GroupOrganisational unit
03811 - Leroux, Jean-Christophe / Leroux, Jean-Christophe
03811 - Leroux, Jean-Christophe / Leroux, Jean-Christophe
Related publications and datasets
Is cited by: https://doi.org/10.3929/ethz-b-000447272
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Show all metadata
Citations
Cited 27 times in
Web of Science
Cited 27 times in
Scopus
ETH Bibliography
yes
Altmetrics