CD10
Synonyms
EC:3.4.24.11, MME, Enkephalinase, CALLA, Neutral endopeptidase, Common acute lymphocytic leukemia antigen, Neprilysin, CD10, Membrane Metalloendopeptidase, Neutral Endopeptidase 24.11, Atriopeptidase, NEP, SFE, Membrane Metallo-Endopeptidase (Neutral Endopeptidase, Enkephalinase, CALLA, CD10), Membrane Metallo-Endopeptidase Variant 1, Membrane Metallo-Endopeptidase Variant 2, Neprilysin-390, Neprilysin-411, CD10 Antigen, EC 3.4.24.11, CMT2T, SCA43, EPN, EC 3.4.24, Skin fibroblast elastase
Description
Neprilysin (MME) has thermolysin-like specificity, but is almost confined on acting on polypeptides of up to 30 amino acids. It has the biological significance in the destruction of opioid peptides such as Met- and Leu-enkephalins by cleavage of a Gly-Phe bond. It is able to cleave angiotensin-1, angiotensin-2 and angiotensin 1-9, and involved in the degradation of atrial natriuretic factor (ANF). It displays UV-inducible elastase activity toward skin preelastic and elastic fibers.
KO Status
RenMab: F1 (+/-)
RenLite: F1 (+/-)
Drug Information
Launched drugs: 2
Drugs in clinical trials: 5
Latest Research Phase: Approved
Drug Name
Code
Phase
Company
Indications
Clinical Trials
Sacubitril/Valsartan Sodium Hydrate
LCZ-696
Approved
Novartis Pharma Ag
Erectile Dysfunction, Heart Failure, Myocardial Infarction, Renal Insufficiency, Postmyocardial Infarction Syndrome, Cardiomyopathy, Hypertrophic, Hypertension, Essential Hypertension, Hepatic Insufficiency, Lymphoma, Ventricular Dysfunction, Left, Heart Failure, Systolic
Racecadotril
Tiorfan, Hidrasec
Approved
Bioprojet Pharma
Diarrhea, Infantile, Diarrhea
Dexecadotril
Phase 3 Clinical
Bioprojet Pharma
Gastrointestinal Diseases
STR-324
STR-324
Phase 2 Clinical
Shanghai Pasteur Institute Of Chinese Academy Of Sciences
Pain, Acute Pain
Sacubitril/Allisartan Isoproxil
S-086, AHU-377/
Phase 2 Clinical
Shenzhen Salubris Pharmaceuticals Co Ltd
Heart Failure, Hypertension, Essential Hypertension
LHW-090
LHV-527, LHW-090
Phase 2 Clinical
Novartis Pharma Ag
Hypertension, Renal Insufficiency, Chronic
Debio-0827
PL-37, Debio-0827
Phase 2 Clinical
Pharmaleads
Pain
Sacubitril
AHU-377
Phase 2 Clinical
Novartis Pharma Ag
Heart Failure, Cardiomyopathy, Hypertrophic, Hypertension, Essential Hypertension
Candoxatrilat
UK-73967
Pending
Pfizer Pharmaceuticals Ltd (China)
Renal Insufficiency, Heart Failure
TD-1439
TD-1439
Pending
Theravance Biopharma
Kidney Diseases
References
Title
Authors
Source
N-terminal domain of Bothrops asper Myotoxin II enhances the activity of endothelin converting enzyme-1 and neprilysin
Smith A.I., Rajapakse N.W., Kleifeld O., Lomonte B., Sikanyika N.L., Spicer A.J., Hodgson W.C., Conroy P.J., Small D.H., Kaye D.M., Parkington H.C., Whisstock J.C., Kuruppu S.,
Sci. Rep. 6:22413-22413(2016)
Corrigendum: N-terminal domain of Bothrops asper Myotoxin II enhances the activity of endothelin converting enzyme-1 and neprilysin
Smith A.I., Rajapakse N.W., Kleifeld O., Lomonte B., Sikanyika N.L., Spicer A.J., Hodgson W.C., Conroy P.J., Small D.H., Kaye D.M., Parkington H.C., Whisstock J.C., Kuruppu S.,
Sci. Rep. 6:24333-24333(2016)
Structure of human neutral endopeptidase (Neprilysin) complexed with phosphoramidon
Oefner C., D'Arcy A., Hennig M., Winkler F.K., Dale G.E.,
J. Mol. Biol. 296:341-349(2000)
Structural analysis of neprilysin with various specific and potent inhibitors
Oefner C., Roques B.P., Fournie-Zaluski M.-C., Dale G.E.,
Acta Crystallogr. D 60:392-396(2004)
Structural studies of a bifunctional inhibitor of neprilysin and DPP-IV
Oefner C., Pierau S., Schulz H., Dale G.E.,
Acta Crystallogr. D 63:975-981(2007)
Molecular cloning and amino acid sequence of human enkephalinase (neutral endopeptidase)
Malfroy B., Kuang W.-J., Seeburg P.H., Mason A.J., Schofield P.R.,
FEBS Lett. 229:206-210(1988)
Hydrolysis of alpha-human atrial natriuretic peptide in vitro by human kidney membranes and purified endopeptidase-24.11. Evidence for a novel cleavage site
Vanneste Y., Michel A., Dimaline R., Najdovski T., Deschodt-Lanckman M.,
Biochem. J. 254:531-537(1988)
Endopeptidase-24.11 in human plasma degrades atrial natriuretic factor (ANF) to ANF(99-105/106-126)
Yandle T.G., Brennan S.O., Espiner E.A., Nicholls M.G., Richards A.M.,
Peptides 10:891-894(1989)
Asp650 is crucial for catalytic activity of neutral endopeptidase 24-11
Le Moual H., Dion N., Roques B.P., Crine P., Boileau G.,
Eur. J. Biochem. 221:475-480(1994)
Identification and quantification of N-linked glycoproteins using hydrazide chemistry, stable isotope labeling and mass spectrometry
Zhang H., Li X.-J., Martin D.B., Aebersold R.,
Nat. Biotechnol. 21:660-666(2003)