Neprilysin (NEP) and NEP2 are membrane-bound zinc metalloproteases. Phosphoramidon is a natural and potent inhibitor of NEP and NEP2, with Ki values of 2 nM for both enzymes. It is also a weak inhibitor of the related zinc metalloprotease endothelin-converting enzyme (Ki = 3.5 μM). Phosphoramidon has little or no effect on a variety of other proteases, including trypsin, papain, chymotrypsin, pepsin, and angiotensin-converting enzyme.
