Merck
  • 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
摘要

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.

材料
货号
品牌
产品描述

Sigma-Aldrich
Trizma ® 碱, Primary Standard and Buffer, ≥99.9% (titration), crystalline
Sigma-Aldrich
人血清, from human male AB plasma, USA origin, sterile-filtered
Sigma-Aldrich
HEPES, ≥99.5% (titration)
Sigma-Aldrich
甲醛 溶液, for molecular biology, 36.5-38% in H2O
Supelco
一水磷酸二氢钠, for analysis EMSURE® ACS,Reag. Ph Eur
Sigma-Aldrich
钙含量检测试剂盒(比色法), sufficient for 250 colorimetric tests
Sigma-Aldrich
十二烷基硫酸钠, ≥98.0% (GC)
Millipore
肌醇 -肌醇, suitable for microbiology, ≥99.0%
Millipore
柠檬酸镁 九水合物, ≥95.0% (KT), suitable for microbiology
Sigma-Aldrich
柠檬酸镁, AldrichCPR
Supelco
棕色储存瓶, volume 240 mL, O.D. × H 61 mm × 143 mm, thread for 24-400, bottle only, pkg of 12 ea
Sigma-Aldrich
内消旋 -四苯基卟啉, BioReagent, suitable for fluorescence, ≥99.0% (HPLC)