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

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 a

SUBMITTER: Schantl AE 

PROVIDER: S-EPMC7002685 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature