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Neprilysin

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Definition: Enzyme that is a major constituent of kidney brush-border membranes and is also present to a lesser degree in the brain and other tissues. It preferentially catalyzes cleavage at the amino group of hydrophobic residues of the B-chain of insulin as well as opioid peptides and other biologically active peptides. The enzyme is inhibited primarily by EDTA, phosphoramidon, and thiorphan and is reactivated by zinc. Neprilysin is identical to common acute lymphoblastic leukemia antigen (CALLA Antigen), an important marker in the diagnosis of human acute lymphocytic leukemia. There is no relationship with CALLA PLANT.      Other names Membrane Metallo-Endopeptidase; Kidney-Brush-Border Neutral Proteinase; Enkephalinase; Enkephalin Dipeptidyl Carboxypeptidase; Endopeptidase-24.11; Common Acute Lymphoblastic Leukemia Antigens; CD10 Antigens; CALLA Antigen; Antigens, Leukemia, Common Acute Lymphoblastic; Antigens, CD10; YGG Forming Enzyme; Thermolysin Like Metalloendopeptidase; Neutral Proteinase, Kidney-Brush-Border; Metalloendopeptidase, Thermolysin-Like; Metallo-Endopeptidase, Membrane; Membrane Metallo Endopeptidase; Kidney Brush Border Neutral Proteinase; Enzyme, YGG-Forming; Enkephalinase 24.11; Endopeptidase, Neutral
 
SubstanceCAS Registry & nameCategoriesSourceDrugs*
NEP-2 protein, C elegans  EC 3.4.24.11   *Neprilysin *Caenorhabditis elegans Proteins. Science. 2010 Sep 24;329(5999):1647-50
3-(1-biphenyl-4-ylmethyl-3-ethoxycarbonyl-1-butylcarbamoyl)propionate-3'-methyl-2'-(pentanoyl(2'-(tetrazol-5-ylate)biphenyl-4'-ylmethyl)amino)butyrate  0   *Aminobutyric Acids *Tetrazoles Receptors, Angiotensin/antagonists & inhibitors Neprilysin/antagonists & inhibitors. Lancet 2010 Apr 10;375(9722):1255-66
CGS 37808  0   *Dipeptides Neprilysin/antagonists & inhibitors. J Cardiovasc Pharmacol 2004 Nov;44 Suppl 1:S211-5
neprilysin 2, mouse  EC 3.4.24.11   *Neprilysin. Mol Cell Biochem 2008 Jun;313(1-2):103-11
AR60 compound  0   *Phosphinic Acids Aspartic Acid/*analogs & derivatives Neprilysin/antagonists & inhibitors. Angew Chem Int Ed Engl 2005 Jun 27;44(26):4058-61
AR58 compound  0   *Phosphinic Acids Aspartic Acid/*analogs & derivatives Neprilysin/antagonists & inhibitors. Angew Chem Int Ed Engl 2005 Jun 27;44(26):4058-61
2-(1-((2-ethyl-1,3,4-thiadiazol-5-yl)aminocarbonyl)cyclopentyl)pentanoic acid  0   *Pentanoic Acids *Thiadiazoles Neprilysin/antagonists & inhibitors. J Med Chem 2006 Jul 13;49(14):4409-24
3-(1-((2-ethyl-1,3,4-thiazol-5-yl)aminocarbonyl)cyclopent-1-yl)-2-propylpropionic acid  0   *Pentanoic Acids *Thiadiazoles Neprilysin/antagonists & inhibitors. Chem Biol Drug Des 2006 Jan;67(1):74-7
N-(2-(mercaptomethyl)-3-methylbutanoyl)-4-(1H-pyrazol-1-yl)phenylalanine  0   *Pyrazoles Phenylalanine/*analogs & derivatives Peptidyl-Dipeptidase A/antagonists & inhibitors Neprilysin/antagonists & inhibitors. J Pharmacol Exp Ther 2005 Dec;315(3):1306-13
2-(2-(5-bromoindan-1-yl)-3-mercaptopropionylamino)-3-(1H-pyrrolo(2,3-b)pyridin-3-yl)propionic acid  0   *Indans Alanine/*analogs & derivatives Peptidyl-Dipeptidase A/antagonists & inhibitors Neprilysin/antagonists & inhibitors. J Pept Res 2004 Feb;63(2):99-107
7-((2-(acetylthio)-1-oxo-3-methylpropyl)amino)-1,2,3,4,6,7,8,12b-octahydro-6-oxopyrido(2,1-a)(2)benzazepin-4-carboxyacid  0   *Benzazepines *Pyridines Peptidyl-Dipeptidase A/antagonists & inhibitors Neprilysin/antagonists & inhibitors. Cardiovasc Res 2003 Nov 1;60(2):447-54
neprilysin 2, rat  EC 3.4.24.11   *Neprilysin. Neuroscience 2003;118(3):627-39
endopeptidase 24.11, Bombyx  EC 3.4.24.-   *Neprilysin Zinc Fingers. Insect Biochem Mol Biol 2001 Nov 1;31(12):1213-9
MMEL1 protein, human  EC 3.4.24.11   *Neprilysin. DNA Cell Biol 2001 Aug;20(8):493-8
SLV 306  0   *Benzazepines Neprilysin/antagonists & inhibitors. Trends Pharmacol Sci 2000 Feb;21(2):38-40
ER 40133  0   *Azepines *Thiazoles Neprilysin/antagonists & inhibitors. J Toxicol Sci 1999 Feb;24(1):45-53
S 21402-1  0   *Propionates *Sulfhydryl Compounds Neprilysin/antagonists & inhibitors. J Pharmacol Exp Ther 1998 Mar;284(3):799-805
3-(2-benzyl-3-(propionylthio)propionyl)amino-5-methybenzoic acid  0   *Sulfhydryl Compounds *Benzoic Acids Neprilysin. Jpn J Pharmacol1997 Dec;75(4):337-46
RB25 compound  0   *Benzylidene Compounds Glycine/*analogs & derivatives Neprilysin/antagonists & inhibitors. Adv Exp Med Biol 1997;421:93-9
ONO 9902  0   *Enkephalins Neprilysin/antagonists & inhibitors Analgesics, Non-Narcotic. Bioorg Med Chem. 1998 Apr;6(4):441-63; Can J Anaesth 1996 Nov;43(11):1175-9
BMS 182657  0   *Benzazepines Neprilysin/antagonists & inhibitors. J Pharmacol Exp Ther 1995 Nov;275(2):745-52
CGS 26303  154116-31-1 Phosphonic acid, (((2-(1,1'-biphenyl)-4-yl-1-(1H-tetrazol-5-yl)ethyl)amino)methyl)-, (S)  *Phosphonic Acids *Tetrazoles Neprilysin/antagonists & inhibitors. Biochem Biophys Res Commun 1994 Oct 14;204(1):407-12
UK 77568  0   Organic Chemicals Protease Inhibitors Neprilysin/antagonists & inhibitors. Clin Exp Pharmacol Physiol 1994 Apr;21(4):307-9
CGS 24128  147861-76-5 beta-Alanine, N-(3-(1,1'-biphenyl)-4-yl-N-(phosphonomethyl)alanyl)  *Phosphonic Acids beta-Alanine/*analogs & derivatives Neprilysin/antagonists & inhibitors. J Cardiovasc Pharmacol 1994 Mar;23(3):358-64
mixanpril  156039-69-9 L-Alanine, N-(2-((benzoylthio)methyl)-1-oxo-3-phenylbutyl)-, (S-(R*,S*))  Alanine/*analogs & derivatives Neprilysin/antagonists & inhibitors. Proc Natl Acad Sci U S A 1994 Apr 26;91(9):4072-6
N-(2-(mercaptomethyl)-3-phenylbutanoyl)-L-alanine  155895-89-9   Alanine/*analogs & derivatives Neprilysin/antagonists & inhibitors. J Med Chem 1994 Apr 15;37(8):1070-83
CGS 25462  147862-03-1 beta-Alanine, N-(3-(1,1'-biphenyl)-4-yl-N-((diphenoxyphosphinyl)methyl)-L-alanyl)  *Biphenyl Compounds *Phosphonic Acids Neprilysin/antagonists & inhibitors. J Med Chem 1994 Feb 18;37(4):498-511
CGS 24592  0   *Phosphonic Acids Phenylalanine/*analogs & derivatives Neprilysin/antagonists & inhibitors. J Med Chem 1994 Feb 18;37(4):498-511
MDL 100173  142695-09-8   *Benzazepines *Pyridines Stereoisomerism Neprilysin/antagonists & inhibitors. J Pharmacol Exp Ther 1994 Jan;268(1):180-6
MDL 100240  142695-08-7   *Benzazepines *Pyridines Stereoisomerism Neprilysin/antagonists & inhibitors. J Pharmacol Exp Ther 1994 Jan;268(1):180-6
6-(mercaptomethyl)-5-oxo-1-thia-4-azacyclotridecane-3-carboxylic acid  150198-30-4   *Peptides, Cyclic Cysteine/*analogs & derivatives Neprilysin/antagonists & inhibitors. J Med Chem 1993 Nov 26;36(24):3829-33
CGS 25155  150126-87-7 L-Proline, 1-((9-((acetylthio)methyl)decahydro-10-oxo-2-azecinyl)carbonyl)-4-hydroxy-, phenylmethyl ester, (2S-(2R*(trans),9S*))  *Hydroxyproline *Peptides, Cyclic Neprilysin/antagonists & inhibitors. J Med Chem 1993 Nov 26;36(24):3821-8
spinorphin  137201-62-8 L-Threonine, N-(N-(1-(N-(N-(N-L-leucyl-L-valyl)-L-valyl)-L-tyrosyl)-L-prolyl)-L-tryptophyl)  *Oligopeptides Neprilysin/antagonists & inhibitors Opioid Peptides. Biochem Biophys Res Commun 1993 Jul 30;194(2):713-9
N-(fluoresceinyl)-N'-(1-(6-(3-mercapto-2-benzyl-1-oxopropyl)amino)-1-hexyl)thiocarbamide  145724-06-7   *Fluoresceins Phenylthiourea/*analogs & derivatives Neprilysin/antagonists & inhibitors. Anal Biochem 1992 Aug 15;205(1):57-64
RB 104  145253-48-1   *Iodobenzenes gamma-Aminobutyric Acid/*analogs & derivatives Neprilysin/antagonists & inhibitors. Proc Natl Acad Sci U S A 1992 July 15;89(14):6388-92
SCH 47896  142621-29-2 beta-Alanine, N-(N-(1-carboxy-3-(4-hydroxyphenyl)propyl)-L-phenylalanyl)-2-hydroxy-, (S-(R*,R*))  *Phenols Phenylalanine/*analogs & derivatives Iodine Radioisotopes Neprilysin/antagonists & inhibitors. J Pharmacol Exp Ther 1992 Jun;261(3):1231-7
N-carboxymethyl-phenylalanylleucine  81109-91-3   *Dipeptides Neprilysin/antagonists & inhibitors. Int J Neurosci 1991 Jul;59(1-3):45-51
retrothiorphan  82154-09-4 Propanoic acid, 3-((1-(mercaptomethyl)-2-phenylethyl)amino)-3-oxo-, (+-)  Thiorphan/*analogs & derivatives Neprilysin/antagonists & inhibitors. J Biol Chem 1992 Feb 5;267(4):2138-41
SCH 42495  136511-43-8   Methionine/*analogs & derivatives Neprilysin/antagonists & inhibitors. J Hypertens Suppl 1990;8(7):S161
alatriopril  135038-57-2 L-Alanine, N-(3-(acetylthio)-2-(1,3-benzodioxol-5-ylmethyl)-1-oxopropyl)-, phenylmethyl ester, (S)  *Dioxoles Alanine/*analogs & derivatives Neprilysin/antagonists & inhibitors. Proc Natl Acad Sci USA 1991;88(10):4210
glycopril  135038-56-1 Glycine, N-(3-(acetylthio)-2-(1,3-benzodioxol-5-ylmethyl)-1-oxopropyl)-, phenylmethyl ester, (S)  *Dioxoles Glycine/*analogs & derivatives Neprilysin/antagonists & inhibitors. Proc Natl Acad Sci USA 1991;88(10):4210
SQ 28603  100845-83-8 beta-Alanine, N-(2-(mercaptomethyl)-1-oxo-3-phenylpropyl)  Alanine/*analogs & derivatives Neprilysin/antagonists & inhibitors.
Pharma Action Enzyme Inhibitors 		Kidney Int 1990;38(1):67
candoxatril  118785-03-8   *Indans *Propionates Prodrugs Neprilysin/antagonists & inhibitors.
Pharma Action Antihypertensive Agents ; Protease Inhibitors 		Br J Pharmacol 1989;98 Suppl:823P
SCH 32615  83861-02-3 beta-Alanine, N-(N-(1-carboxy-2-phenylethyl)-L-phenylalanyl)-, (S)  *Dipeptides Neprilysin/antagonists & inhibitors.
Pharma Action Protease Inhibitors 		J Clin Invest 1990;85(1):170
3-(N-hydroxycarboxamido-2-benzylpropanoyl)phenylalanine  105831-46-7   *Hydroxamic Acids Phenylalanine/*analogs & derivatives Neprilysin/antagonists & inhibitors. Eur J Pharmacol 1989;165(2-3):199
candoxatrilat  123898-42-0 Cyclohexanecarboxylic acid, 4-(((1-(2-carboxy-3-(2-methoxyethoxy)propyl)cyclopentyl)carbonyl)amino)-, cis-(+-)  *Cyclohexanecarboxylic Acids Neprilysin/antagonists & inhibitors.
Pharma Action Protease Inhibitors 		Lancet 1989;2(8663):591
Sch 34826  105262-04-2 beta-Alanine, N-(N-(2-((2,2-dimethyl-1,3-dioxolan-4-yl)methoxy)-2-oxo-1-(phenylmethyl)ethyl)-L-phenylalanyl)  *Dioxolanes *Dipeptides Neprilysin/antagonists & inhibitors.
Pharma Action Analgesics ; Protease Inhibitors 		J Pharmacol Exp Ther 1988;245(3):829
acetorphan  81110-73-8 Glycine, N-(2-((acetylthio)methyl)-1-oxo-3-phenylpropyl)-, phenylmethyl ester, (+-)  Thiorphan/*analogs & derivatives Neprilysin/antagonists & inhibitors.
Pharma Action Antidiarrheals ; Protease Inhibitors 		J Pharmacol Exp Ther 1986;237(3):937
ACTH (4-7), Pro-Gly-Pro  80714-61-0   *Peptide Fragments Adrenocorticotropic Hormone/*analogs & derivatives Neprilysin/antagonists & inhibitors.
Pharma Action Enzyme Inhibitors ; Neuroprotective Agents ; Nootropic Agents 		Biull Eksp Biol Med 1986;101(3):267

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