Merck
  • Home
  • Search Results
  • Inhibition of vascular calcification by inositol phosphates derivatized with ethylene glycol oligomers.

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

Nature communications (2020-02-07)
Antonia E Schantl, Anja Verhulst, Ellen Neven, Geert J Behets, Patrick C D'Haese, Marc Maillard, David Mordasini, Olivier Phan, Michel Burnier, Dany Spaggiari, Laurent A Decosterd, Mark G MacAskill, Carlos J Alcaide-Corral, Adriana A S Tavares, David E Newby, Victoria C Beindl, Roberto Maj, Anne Labarre, Chrismita Hegde, Bastien Castagner, Mattias E Ivarsson, Jean-Christophe Leroux
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.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Human Serum, from human male AB plasma, USA origin, sterile-filtered
Sigma-Aldrich
Calcium Colorimetric Assay, sufficient for 250 colorimetric tests
Sigma-Aldrich
Formaldehyde solution, for molecular biology, 36.5-38% in H2O
Sigma-Aldrich
Trizma® base, Primary Standard and Buffer, ≥99.9% (titration), crystalline
Sigma-Aldrich
HEPES, ≥99.5% (titration)
Millipore
myo-Inositol, suitable for microbiology, ≥99.0%
Sigma-Aldrich
meso-Tetraphenylporphyrin, BioReagent, suitable for fluorescence, ≥99.0% (HPLC)
Sigma-Aldrich
Sodium dodecyl sulfate, ≥98.0% (GC)
Millipore
Magnesium citrate tribasic nonahydrate, ≥95.0% (KT), suitable for microbiology
Supelco
Amber storage bottles, volume 240 mL, O.D. × H 61 mm × 143 mm, thread for 24-400, bottle only, pkg of 12 ea
Sigma-Aldrich
Magnesium citrate, AldrichCPR
Supelco
Sodium dihydrogen phosphate monohydrate, for analysis EMSURE® ACS,Reag. Ph Eur