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/EXP3174

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)