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dc.contributor.author
Schantl, Antonia E.
dc.contributor.author
Verhulst, Anja
dc.contributor.author
Neven, Ellen
dc.contributor.author
Behets, Geert J.
dc.contributor.author
D’Haese, Patrick C.
dc.contributor.author
Maillard, Marc
dc.contributor.author
Mordasini, David
dc.contributor.author
Phan, Olivier
dc.contributor.author
Burnier, Michel
dc.contributor.author
Spaggiari, Dany
dc.contributor.author
Decosterd, Laurent A.
dc.contributor.author
MacAskill, Mark G.
dc.contributor.author
Alcaide-Corral, Carlos J.
dc.contributor.author
Tavares, Adriana A.S.
dc.contributor.author
Newby, David E.
dc.contributor.author
Beindl, Victoria C.
dc.contributor.author
Maj, Roberto
dc.contributor.author
Labarre, Anne
dc.contributor.author
Hegde, Chrismita
dc.contributor.author
Castagner, Bastien
dc.contributor.author
Ivarsson, Mattias E.
dc.contributor.author
Leroux, Jean-Christophe
dc.date.accessioned
2020-02-14T07:52:06Z
dc.date.available
2020-02-14T03:23:16Z
dc.date.available
2020-02-14T07:52:06Z
dc.date.issued
2020
dc.identifier.issn
2041-1723
dc.identifier.other
10.1038/s41467-019-14091-4
en_US
dc.identifier.uri
http://hdl.handle.net/20.500.11850/399364
dc.identifier.doi
10.3929/ethz-b-000399364
dc.description.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.
en_US
dc.format
application/pdf
en_US
dc.language.iso
en
en_US
dc.publisher
Nature Publishing Group
en_US
dc.rights.uri
http://creativecommons.org/licenses/by/4.0/
dc.title
Inhibition of vascular calcification by inositol phosphates derivatized with ethylene glycol oligomers
en_US
dc.type
Journal Article
dc.rights.license
Creative Commons Attribution 4.0 International
dc.date.published
2020-02-05
ethz.journal.title
Nature Communications
ethz.journal.volume
11
en_US
ethz.journal.issue
1
en_US
ethz.journal.abbreviated
Nat Commun
ethz.pages.start
721
en_US
ethz.size
17 p.
en_US
ethz.version.deposit
publishedVersion
en_US
ethz.identifier.scopus
ethz.publication.place
London
en_US
ethz.publication.status
published
en_US
ethz.date.deposited
2020-02-14T03:23:40Z
ethz.source
SCOPUS
ethz.eth
yes
en_US
ethz.availability
Open access
en_US
ethz.rosetta.installDate
2020-02-14T07:52:17Z
ethz.rosetta.lastUpdated
2020-02-14T07:52:17Z
ethz.rosetta.exportRequired
true
ethz.rosetta.versionExported
true
ethz.COinS
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