Description
Phosphoramidon (119942-99-3) inhibits neutral endopeptidase 24.11 (NEP; Neprilysin; EC 3.4.24.11), Ki=2 nM.1?Also inhibits neprilysin 2 (Ki~2 nM).2?Also inhibits endothelin-converting enzyme (IC50?= 0.68 μM).3?Induces a dramatic increase in amyloid-beta levels in rodents.4
Uses
An endothelin-converting enzyme inhibitor, attenuates lipopolysaccharide-induced acute lung injury.
General Description
Phosphoramidon [N-(α-rhamnopyranosyl-oxyhydroxyphosphinyl)-Leu-Trp] is a competitive inhibitor of several soluble zinc metalloproteases. Phosphoramidate is produced naturally by Streptomyces?tanashiensis.
Biological Activity
Inhibits neutral endopeptidase 24.11 (NEP, neprilysin; EC 3.4.24.11) (Ki=2nM), a cell surface zinc metalloprotease which cleaves bioactive peptides such as bradykinin, neurotensin, and enkephalin. Also inhibits neprilysin 2 (Ki~2nM). Potent inhibitor of endothelin-converting enzyme (ECE) (IC50=0.68μM).
Biochem/physiol Actions
Phosphoramidon can inhibit ZMPSTE24, an integral membrane protein zinc metalloprotease. It is capable of blocking thermolysin.
References
1) Stephenson and Kenny et al. (1987),?The hydrolysis of alpha-human atrial natriuretic peptide by pig kidney microvillar membranes is initiated by endopeptidase-24.11.; Biochem. J.,?243?183.
2) Rose?et al.?(2002),?Cell-specific activity of neprilysin 2 isoforms and enzymic specificity compared with neprilysin; Biochem. J.,?363?697
3) Ahn?et al.?(1998),?Soluble human endothelin-converting enzyme-1: expression, purification, and demonstration of pronounced pH sensitivity; Arch. Biochem. Biphys.,?359?258
4) Marr and Hafez (2014),?Amyloid-beta and Alzheimer’s disease: the role of neprilysin-2 in amyloid-beta clearance; Front. Aging Neurosci.,?6?187
