Phosphoramidon (Disodium)

164204-38-0

C23H32N3Na2O10P

H2O : >= 140 mg/mL (238.31 mM)

Metabolic Enzyme/Protease; Metabolic Enzyme/Protease

Phosphoramidon Disodium is a metalloprotease inhibitor. Phosphoramidon inhibits endothelin-converting enzyme (ECE), neutral endopeptidase (NEP), and angiotensin-converting enzyme (ACE) with IC₅₀ values of 3.5, 0.034, and 78 uM, respectively. IC50 & Target: IC50: 3.5 uM (ECE), 34 nM (NEP), 78 uM (ACE)^[1] In Vitro: Phosphoramidon is a naturally occurring glycopeptide first isolated from a strain of Streptomyces tanashiensis. It has a unique chemical structure featuring a phosphoramidate linkage between a-L-rhamnose and L-leucineL-tryptophan. As a microbial metabolite, phosphoramidon exhibits potent inhibitory activity against thermolysin, a zinc endopeptidase isolated from Bacillus thermoproteolyticus (K_i=32 nM)^[2]. In Vivo: Intranasal administration of phosphoramidon produces significantly elevated cerebral Abeta levels in wild-type mice. Furthermore, intranasal phosphoramidon administration in double knockout mice lacking NEP and NEP2 also shows increased levels of Abeta40^[3]. Phosphoramidon blocks the formation of endothelin-1 (ET-1), a proinflammatory mediator implicated in the pathogenesis of a variety of lung diseases. Phosphoramidon significantly reduces LPS-induced pulmonary inflammation as measured by lung histology, neutrophil content of bronchoalveolar lavage (BAL) fluid, percent tumor necrosis factor receptor 1 (TNFR1)-labeled BAL macrophages, and alveolar septal cell apoptosis^[4]. Phosphoramidon significantly decreased ET-1 levels, causing a concomitant big ET-1 increase and dose-dependently attenuated indomethacin-induced gastric mucosal damage^[5].