We describe N-[(2S)-2-(mercaptomethyl)-3-methylbutanoyl]-4-(1H-pyrazol-1-yl)-L-phenylalanine (GW796406), a vasopeptidase inhibitor (VPI) that possessed approximately 3-fold selectivity for neutral endopeptidase 24.11 (NEP) versus angiotensin-converting enzyme (ACE) in in vitro assays using rat and human enzymes. In the same assays, omapatrilat, the most extensively studied VPI, displayed approx...

Neprilysin, also known as neutral endopeptidase (NEP), endopeptidase 24.11, CD10, enkephalinase, and common acute lymphoblastic leukemia antigen (CALLA), is a membrane-bound metalloendopeptidase (EC 3.4.24.11) that has recently sprung to renewed prominence as a target in cardiovascular therapeutics. Numbered among the many substrates to NEP are multiple vasoactive peptides, including the cardia...

BACKGROUND AND PURPOSE Although myelin-associated neurite outgrowth disinhibitors have shown promise in restoring motor function after stroke, their interactive effects with motor training have rarely been investigated. The present study examined whether a combinatorial treatment (NEP 1-40+motor rehabilitation) is more effective than either treatment alone in promoting motor recovery after foca...

Neprilysin (NEP) is an endogenous protease that degrades a wide range of peptides including amyloid beta (Aβ), the main pathological component of Alzheimer's disease (AD). We have engineered NEP as a potential therapeutic for AD but found in pre-clinical safety testing that this variant increased prothrombin time (PT) and activated partial thromboplastin time (APTT). The objective of the curren...

Influenza virus is a major human and animal pathogen causing seasonal epidemics and occasional pandemics in the human population that are associated with significant morbidity and mortality. Influenza A virus, a member of the orthomyxovirus family, contains an RNA genome with a coding capacity for a limited number of proteins. In addition to ensuring the structural integrity of virions, these v...

BACKGROUND Trends in Alaska ecosystem carbon fluxes were predicted from inputs of monthly MODerate resolution Imaging Spectroradiometer (MODIS) vegetation index time-series combined with the NASA-CASA (Carnegie Ames Stanford Approach) carbon cycle simulation model over the past decade. CASA simulates monthly net ecosystem production (NEP) as the difference in carbon fluxes between net primary p...

OBJECTIVES Spinal cord stimulation (SCS) is known to be an effective treatment for a range of neuropathic pain (NeP) conditions, although further clinical evidence is required. Clinical observations suggest that 1 aspect of the treatment effect is a reduction in the area with spontaneous NeP. The aim of this study was to quantify the areas of spontaneous NeP in SCS patients and to correlate the...

Atrial natriuretic factor (ANF) is degraded by neutral endopeptidase. We hypothesized that neutral endopeptidase inhibition (NEP-I) increases sodium excretion and that this effect would be potentiated in the presence of an isolated increase in intrarenal ANF. In seven anesthetized dogs, ANF was infused into one renal artery to produce pathophysiologic concentrations in the supplemented kidney w...