Information on EC 3.4.24.11 - neprilysin

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The expected taxonomic range for this enzyme is: Eukaryota, Bacteria

EC NUMBER
COMMENTARY
3.4.24.11
-
RECOMMENDED NAME
GeneOntology No.
neprilysin
REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
preferential cleavage of polypeptides between hydrophobic residues, particularly with Phe or Tyr at P1'
show the reaction diagram
-
-
-
-
REACTION TYPE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
hydrolysis of peptide bond
-
-
hydrolysis of peptide bond
-
-
hydrolysis of peptide bond
-
-
endopeptidase; peptides, endopeptidase
-
SYNONYMS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
acute lymphoblastic leukemia antigen
-
-
antigen, CALLA (common acute lymphoblastic leukemia-associated)
-
-
-
-
CALLA
-
-
-
-
CALLA
-
-
CALLA (common acute lymphoblastic leukemia-associated) antigens
-
-
-
-
CALLA antigen
-
-
-
-
CALLA glycoproteins
-
-
-
-
CD10
-
-
-
-
CD10
-
-
CD10/neutral endopeptidase
-
-
CD10/neutral endopeptidase 24.11
-
-
common acute lymphoblastic leukemia antigen
-
-
common acute lymphoblastic leukemia-associated antigens
-
-
-
-
Common acute lymphocytic leukemia antigen
-
-
-
-
endopeptidase CD10
-
-
Endopeptidase-2
-
-
-
-
endopeptidase-24.11
-
-
-
-
enkephalinase
-
-
-
-
enkephalinase
-
-
enkephalinase
-
-
EP24.11
-
-
glycoprotein, CALLA
-
-
-
-
kidney-brush-border neutral endopeptidase
-
-
-
-
kidney-brush-border neutral peptidase
-
-
-
-
kidney-brush-border neutral proteinase
-
-
-
-
membrane metalloendopeptidase
-
-
-
-
NEP
-
-
-
-
NEP
-
-
NEP
-
-
NEP 24.11
-
-
NEP, enkephalinase, neutrophil cluster-differentiation antigen 10, common acute lymphoblastic leukemia antigen
-
-
NEP/CD10
-
-
NEP2
-
-
neprilypsin
-
-
neprilysin
-
-
neprilysin
-
-
neprilysin 4
-, Q9I7I4
two isoforms exist due to different splice-variants: larger isoform A is expressed as a membrane bound protein and isoform B lacking the N-terminal cytosolic and transmembrane region is expressed as a soluble protein
neutral endopeptidase
-
-
-
-
neutral endopeptidase
-
-
neutral endopeptidase
-
-
neutral endopeptidase
-
-
neutral endopeptidase
-
-
neutral endopeptidase
-
-
neutral endopeptidase 24.11
-
-
-
-
neutral endopeptidase 24.11
-
-
neutral endopeptidase 24.11/CD10
-
-
neutral metallendopeptidase
-
-
-
-
NL-1
-
-
peptidase, endo-
-
-
-
-
peptidase, membrane metalloendo-
-
-
-
-
CAS REGISTRY NUMBER
COMMENTARY
82707-54-8
-
ORGANISM
COMMENTARY
LITERATURE
SEQUENCE CODE
SEQUENCE DB
SOURCE
expression in Drosophila melanogaster
-
-
Manually annotated by BRENDA team
expression in mouse
-
-
Manually annotated by BRENDA team
patients with prostate cancer
-
-
Manually annotated by BRENDA team
transgenic expression in mouse
-
-
Manually annotated by BRENDA team
SW strain and C57B1/6J strain
-
-
Manually annotated by BRENDA team
adult male Wilstar
-
-
Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
malfunction
-
the role of NEP in neuropathy related to either insulin-deficient diabetes or diet-induced obesity using NEP deficient (-/-) mice is explored. Glucose disposal is impaired in both C57Bl/6 and NEP -/- mice fed a high fat diet. Thermal hypoalgesia and nerve conduction slowing are present in both streptozotocin-diabetic and high fat fed C57Bl/6 mice but not in NEP -/- mice exposed to either streptozotocin-induced diabetes or a high fat diet
malfunction
-
following overexpression of neprilysin using an adenovirus encoding neprilysin islet amyloid deposition and beta-cell apoptosis both decrease by 79%
malfunction
-
amyloid-beta concentrations are elevated in the brains of NEP knockout mice at all investigated age groups, but immunohistochemical analysis using monoclonal antibodies do not detect any amyloid-beta deposits even in old NEP knockout mice. Tests of learning and memory reveal that the ability to learn is not reduced in old NEP-deficient mice but instead have significantly improved. Data suggests a beneficial effect of pharmacological inhibition of cerebral NEP on learning and memory in mice due to the accumulation of peptides other than amyloid-beta degradable by NEP
malfunction
-
in NEP/NEP2 double-knockout mice, amyloid-beta peptide levels are marginally increased (1.5 to 2fold), compared with NEP-/-/NEP2+/+ controls. Treatment of these double-knockout mice with phosphoramidon results in elevations of amyloid-beta peptide, suggesting that yet other NEP-like amyloid-beta peptide -degrading endopeptidases are contributing to amyloid-beta peptide catabolism
physiological function
-
neprilysin decreases islet amyloid deposition by inhibiting human islet amyloid polypeptide fibril formation, rather than degrading human islet amyloid polypeptide
physiological function
-
inhibition of NEP by the opiorphin homologs influence the physiology of a wide variety of tissues by causing extended binding time of peptide agonists to their receptors such as G-protein-coupled receptors (GPCRs)
physiological function
-
CD10, a cell-surface neutral endopetidase, is involved in the maintenance of homeostasis, in neoplastic transformation, and in tumor progression through the enzymatic inactivation of bioactive peptides. CD10 is suggested to function as a tumor-suppressor gene, and to inactivate neuropeptide growth factors implicated in cancer progression; molecular interactions between arsenic microcrystals and membrane-bound CD10 to be implicated in arsenic-induced carcinogenesis
physiological function
-
a genetic case-control association study is performed investigating GT-repeat polymorphism in the NEP promoter region as well as 18 tag-SNPs in six linkage disequilibrium blocks in the NEP gene region in a large sample of complex regional pain syndrome patients. No significant genetic association is observed
SUBSTRATE
PRODUCT                      
REACTION DIAGRAM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
(Substrate)
LITERATURE
(Substrate)
COMMENTARY
(Product)
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
2-aminobenzoyl-ARFK-2,4-dinitrophenyl ester + H2O
2-aminobenzoyl-AR + FK-2,4-dinitrophenyl ester
show the reaction diagram
-
-
-
-
ir
2-aminobenzoyl-DRFK-2,4-dinitrophenyl ester + H2O
2-aminobenzoyl-DR + FK-2,4-dinitrophenyl ester
show the reaction diagram
-
-
-
-
ir
2-aminobenzoyl-FRFK-2,4-dinitrophenyl ester + H2O
2-aminobenzoyl-FR + FK-2,4-dinitrophenyl ester
show the reaction diagram
-
-
-
-
ir
2-aminobenzoyl-HRFK-2,4-dinitrophenyl ester + H2O
2-aminobenzoyl-HR + FK-2,4-dinitrophenyl ester
show the reaction diagram
-
-
-
-
ir
2-aminobenzoyl-IRFK-2,4-dinitrophenyl ester + H2O
2-aminobenzoyl-IR + FK-2,4-dinitrophenyl ester
show the reaction diagram
-
-
-
-
ir
2-aminobenzoyl-KRFK-2,4-dinitrophenyl ester + H2O
2-aminobenzoyl-KR + FK-2,4-dinitrophenyl ester
show the reaction diagram
-
-
-
-
ir
2-aminobenzoyl-LRFK-2,4-dinitrophenyl ester + H2O
2-aminobenzoyl-LR + FK-2,4-dinitrophenyl ester
show the reaction diagram
-
-
-
-
ir
2-aminobenzoyl-NRFK-2,4-dinitrophenyl ester + H2O
2-aminobenzoyl-NR + FK-2,4-dinitrophenyl ester
show the reaction diagram
-
-
-
-
ir
2-aminobenzoyl-RAFK-2,4-dinitrophenyl ester + H2O
2-aminobenzoyl-RA + FK-2,4-dinitrophenyl ester
show the reaction diagram
-
-
-
-
ir
2-aminobenzoyl-RDFK-2,4-dinitrophenyl ester + H2O
2-aminobenzoyl-RD + FK-2,4-dinitrophenyl ester
show the reaction diagram
-
-
-
-
ir
2-aminobenzoyl-REFK-2,4-dinitrophenyl ester + H2O
2-aminobenzoyl-RE + FK-2,4-dinitrophenyl ester
show the reaction diagram
-
-
-
-
ir
2-aminobenzoyl-rGF-N-(2,4-dinitrophenyl)ethylenediamine + H2O
2-aminobenzoyl-D-Arg-Gly + Phe-N-(2,4-dinitrophenyl)ethylenediamine
show the reaction diagram
-
-
-
-
ir
2-aminobenzoyl-RGFK(Dnp)-OH + H2O
2-aminobenzoyl-RG + FK-2,4-dinitrophenyl ester
show the reaction diagram
-
-
-
-
ir
2-aminobenzoyl-RGFK-2,4-dinitrophenyl amide + H2O
2-aminobenzoyl-RG + FK-2,4-dinitrophenyl amide
show the reaction diagram
-
-
-
-
ir
2-aminobenzoyl-RGFK-2,4-dinitrophenyl ester + H2O
2-aminobenzoyl-RG + FK-2,4-dinitrophenyl ester
show the reaction diagram
-
-
-
-
ir
2-aminobenzoyl-rGL-N-(2,4-dinitrophenyl)ethylenediamine + H2O
2-aminobenzoyl-D-Arg-Gly + Leu-N-(2,4dinitrophenyl)ethylenediamine
show the reaction diagram
-
-
-
-
ir
2-aminobenzoyl-rGV-N-(2,4-dinitrophenyl)ethylenediamine + H2O
2-aminobenzoyl-D-Arg-Gly + Val-N-(2,4-dinitrophenyl)ethylenediamine
show the reaction diagram
-
-
-
-
ir
2-aminobenzoyl-RHFK-2,4-dinitrophenyl ester + H2O
2-aminobenzoyl-RH + FK-2,4-dinitrophenyl ester
show the reaction diagram
-
-
-
-
ir
2-aminobenzoyl-RKFK-2,4-dinitrophenyl ester + H2O
2-aminobenzoyl-RK + FK-2,4-dinitrophenyl ester
show the reaction diagram
-
-
-
-
ir
2-aminobenzoyl-RNFK-2,4-dinitrophenyl ester + H2O
2-aminobenzoyl-RN + FK-2,4-dinitrophenyl ester
show the reaction diagram
-
-
-
-
ir
2-aminobenzoyl-RPFK-2,4-dinitrophenyl ester + H2O
2-aminobenzoyl-RP + FK-2,4-dinitrophenyl ester
show the reaction diagram
-
-
-
-
ir
2-aminobenzoyl-RQFK-2,4-dinitrophenyl ester + H2O
2-aminobenzoyl-RQ + FK-2,4-dinitrophenyl ester
show the reaction diagram
-
-
-
-
ir
2-aminobenzoyl-RRFK-2,4-dinitrophenyl amide + H2O
2-aminobenzoyl-RR + FK-2,4-dinitrophenyl amide
show the reaction diagram
-
-
-
-
ir
2-aminobenzoyl-RRFK-2,4-dinitrophenyl ester + H2O
2-aminobenzoyl-RG + FK-2,4-dinitrophenyl ester
show the reaction diagram
-
-
-
-
ir
2-aminobenzoyl-RRFK-2,4-dinitrophenyl ester + H2O
2-aminobenzoyl-RR + FK-2,4-dinitrophenyl ester
show the reaction diagram
-
-
-
-
ir
2-aminobenzoyl-rRL-N-(2,4-dinitrophenyl)ethylenediamine + H2O
2-aminobenzoyl-D-Arg-L-Arg + Leu-N-(2,4-dinitrophenyl)ethylenediamine
show the reaction diagram
-
-
-
-
ir
2-aminobenzoyl-RSFK-2,4-dinitrophenyl ester + H2O
2-aminobenzoyl-RS + FK-2,4-dinitrophenyl ester
show the reaction diagram
-
-
-
-
ir
2-aminobenzoyl-rSL-N-(2,4-dinitrophenyl)ethylenediamine + H2O
2-aminobenzoyl-D-Arg-L-Ser + Leu-N-(2,4-dinitrophenyl)ethylenediamine
show the reaction diagram
-
-
-
-
ir
2-aminobenzoyl-RTFK-2,4-dinitrophenyl ester + H2O
2-aminobenzoyl-RT + FK-2,4-dinitrophenyl ester
show the reaction diagram
-
-
-
-
ir
2-aminobenzoyl-SRFK-2,4-dinitrophenyl ester + H2O
2-aminobenzoyl-SR + FK-2,4-dinitrophenyl ester
show the reaction diagram
-
-
-
-
ir
2-aminobenzoyl-TRFK-2,4-dinitrophenyl ester + H2O
2-aminobenzoyl-TR + FK-2,4-dinitrophenyl ester
show the reaction diagram
-
-
-
-
ir
2-aminobenzoyl-VRFK-2,4-dinitrophenyl ester + H2O
2-aminobenzoyl-VR + FK-2,4-dinitrophenyl ester
show the reaction diagram
-
-
-
-
ir
2-aminobenzoyl-WRFK-2,4-dinitrophenyl ester + H2O
2-aminobenzoyl-WR + FK-2,4-dinitrophenyl ester
show the reaction diagram
-
-
-
-
ir
2-aminobenzoyl-YRFK-2,4-dinitrophenyl ester + H2O
2-aminobenzoyl-YR + FK-2,4-dinitrophenyl ester
show the reaction diagram
-
-
-
-
ir
adrenocorticotropic hormone + H2O
?
show the reaction diagram
-
-
-
-
?
Aldolase + H2O
?
show the reaction diagram
-
-
-
-
?
alpha-neoendorphin + H2O
?
show the reaction diagram
-
-
-
-
?
alpha-neoendorphin + H2O
?
show the reaction diagram
-
-
-
-
?
amyloid beta(1-40) mutant A21G + H2O
?
show the reaction diagram
-
Flemish variant of amyloid beta. Decreased degradation by neprilysin compared to either wild-type peptide or the other mutant peptides
-
-
?
amyloid beta(1-40) mutant D23N + H2O
?
show the reaction diagram
-
Iowa variant of amyloid beta
-
-
?
amyloid beta(1-40) mutant E22G + H2O
?
show the reaction diagram
-
Arctic variant of amyloid beta
-
-
?
amyloid beta(1-40) mutant E22K + H2O
?
show the reaction diagram
-
Italian variant of amyloid beta
-
-
?
amyloid beta(1-40) mutant E22Q + H2O
?
show the reaction diagram
-
Dutch variant of amyloid beta
-
-
?
amyloid beta(1-40) peptide + H2O
?
show the reaction diagram
-
-
-
-
?
Angiotensin I + H2O
?
show the reaction diagram
-
-
-
-
?
Angiotensin I + H2O
?
show the reaction diagram
-
-
-
-
?
Angiotensin I + H2O
?
show the reaction diagram
-
-
-
-
?
Angiotensin I + H2O
?
show the reaction diagram
-
-
-
-
?
Angiotensin I + H2O
?
show the reaction diagram
-, Q9I7I4
51.6% degradation
-
-
?
Angiotensin II + H2O
?
show the reaction diagram
-
-
-
-
?
Angiotensin II + H2O
?
show the reaction diagram
-
-
-
-
?
Angiotensin II + H2O
?
show the reaction diagram
-
-
-
-
?
angiotensin III + H2O
?
show the reaction diagram
-
-
-
-
?
angiotensin(1-9) + H2O
?
show the reaction diagram
-
-
-
-
?
Arg-Pro-Lys-Pro-Gln-Gln-Phe-Phe-Gly-Leu-Met-NH2 + H2O
?
show the reaction diagram
-
-
-
-
?
Arg-Pro-Lys-Pro-Gln-Gln-Phe-Phe-Gly-Leu-Met-NH2 + H2O
?
show the reaction diagram
-
-
-
-
?
Arg-Pro-Lys-Pro-Gln-Gln-Phe-Phe-Gly-Leu-Met-NH2 + H2O
?
show the reaction diagram
-
-
-
-
?
Arg-Pro-Lys-Pro-Gln-Gln-Phe-Phe-Gly-Leu-Met-NH2 + H2O
?
show the reaction diagram
-
-
-
-
?
Arg-Pro-Lys-Pro-Gln-Gln-Phe-Phe-Gly-Leu-Met-NH2 + H2O
?
show the reaction diagram
-
-
-
-
?
Arg-Pro-Lys-Pro-Gln-Gln-Phe-Phe-Gly-Leu-Met-NH2 + H2O
?
show the reaction diagram
-
i.e. substance P, seven peptides are produced
-
-
?
Asp-Tyr(SO3H)-Met-Gly-Trp-Met-Asp-PheNH2 + H2O
?
show the reaction diagram
-
-
-
-
?
Asp-Tyr(SO3H)-Met-Gly-Trp-Met-Asp-PheNH2 + H2O
?
show the reaction diagram
-
-
-
-
?
Asp-Tyr(SO3H)-Met-Gly-Trp-Met-Asp-PheNH2 + H2O
?
show the reaction diagram
-
-
-
-
?
Asp-Tyr(SO3H)-Met-Gly-Trp-Met-Asp-PheNH2 + H2O
?
show the reaction diagram
-
-
-
-
?
Asp-Tyr(SO3H)-Met-Gly-Trp-Met-Asp-PheNH2 + H2O
?
show the reaction diagram
-
i.e. cholecystokinin-8, two distinct cleavage sites: Asp-Tyr(SO3H)-Met-Gly-/-Trp-Met-Asp-/-PheNH2, the splitting of the Asp7-Phe8NH2 bond proceeds 4-times more rapidly than the Gly4-Trp5 bond
-
-
?
Atrial natriuretic factor + H2O
?
show the reaction diagram
-
-
-
-
?
Atrial natriuretic factor + H2O
?
show the reaction diagram
-
-
-
-
?
Atrial natriuretic factor + H2O
?
show the reaction diagram
-
-
-
-
?
Atrial natriuretic factor + H2O
?
show the reaction diagram
-
human alpha atrial natriuretic peptide/cardiodilatin shows a single major cleavage site within the disulfide-linked loop between Cys and Phe in position 7 and 8
-
-
?
Atrial natriuretic factor + H2O
?
show the reaction diagram
-
seven sites of hydrolysis: Arg4-Ser5, Cys7-Phe8, Arg11-Met12, Arg14-Ile15, Gly16-Ala17, Gly-20-Leu21, Ser25-Phe26. The initial attack takes place at a bond within the disulfide-linked loop and produces a peptide having the same amino acid composition as intact atrial natriuretic factor
-
-
?
Atrial natriuretic factor + H2O
?
show the reaction diagram
-
dominant enzyme in the hydrolysis of atrial natriuretic factor
-
-
-
atrial natriuretic peptide + H2O
?
show the reaction diagram
-
-
-
-
?
atrial natriuretic peptide + H2O
?
show the reaction diagram
-
no activity with brain natriuretic peptide
-
-
?
azocasein + H2O
?
show the reaction diagram
-
-
-
-
?
Azocoll + H2O
?
show the reaction diagram
-
-
-
-
?
benzoyl-Gly-Gly-Leu-p-nitroanilide + H2O
benzoyl-Gly-Gly + Leu-p-nitroanilide
show the reaction diagram
-
-
-
?
benzyloxycarbonyl-Ala-Gly-Leu-Ala + H2O
?
show the reaction diagram
-
-
-
-
?
benzyloxycarbonyl-Phe-Arg-4-methyl-7-coumarylamide + H2O
?
show the reaction diagram
-
-
-
-
?
beta-amyloid peptide + H2O
?
show the reaction diagram
-
-
-
-
?
beta-lipotropin(61-69) + H2O + H2O
?
show the reaction diagram
-
-
-
-
?
beta-neoendorphin + H2O
?
show the reaction diagram
-
-
-
-
?
beta-neoendorphin + H2O
?
show the reaction diagram
-
-
-
-
?
Bradykinin + H2O
?
show the reaction diagram
-
-
-
-
?
Bradykinin + H2O
?
show the reaction diagram
-
-
-
-
?
Bradykinin + H2O
?
show the reaction diagram
-
-
-
-
?
Bradykinin + H2O
?
show the reaction diagram
-
-
-
-
?
Bradykinin + H2O
?
show the reaction diagram
-
-
-
-
?
Bradykinin + H2O
?
show the reaction diagram
-, Q9I7I4
27.8% degradation
-
-
?
casein + H2O
?
show the reaction diagram
-
-
-
-
?
cholecystokinin-8 + H2O
?
show the reaction diagram
-
-
-
-
-
cholecystokinin-8 + H2O
?
show the reaction diagram
-
-
-
-
?
D-Ala2-Leu5-enkephalin + H2O
Tyr-D-Ala-Gly + Phe-Leu
show the reaction diagram
-
i.e. Tyr-D-Ala-Gly-Phe-Leu
-
-
?
D-Ala2-Leu5-enkephalin + H2O
Tyr-D-Ala-Gly + Phe-Leu
show the reaction diagram
-
i.e. Tyr-D-Ala-Gly-Phe-Leu
-
-
?
D-Ala2-Leu5-enkephalin + H2O
Tyr-D-Ala-Gly + Phe-Leu
show the reaction diagram
-
i.e. Tyr-D-Ala-Gly-Phe-Leu
-
-
?
D-Ala2-Leu5-enkephalin + H2O
Tyr-D-Ala-Gly + Phe-Leu
show the reaction diagram
-
i.e. Tyr-D-Ala-Gly-Phe-Leu
-
-
?
D-Ala2-Leu5-enkephalin + H2O
Tyr-D-Ala-Gly + Phe-Leu
show the reaction diagram
-
i.e. Tyr-D-Ala-Gly-Phe-Leu
-
-
?
D-Ala2-Leu5-enkephalin + H2O
Tyr-D-Ala-Gly + Phe-Leu
show the reaction diagram
-
i.e. Tyr-D-Ala-Gly-Phe-Leu
-
?
D-Ala2-Leu5-enkephalinamide + H2O
?
show the reaction diagram
-
-
-
-
?
dansyl-Gly-Trp-Gly + H2O
dansyl-Gly + Trp-Gly
show the reaction diagram
-
-
-
?
dansyl-Gly-Tyr-Gly + H2O
dansyl-Gly + Tyr-Gly
show the reaction diagram
-
-
-
?
dansyl-Gly-Tyr-Gly-NH2 + H2O
dansyl-Gly + Tyr-Gly-NH2
show the reaction diagram
-
-
-
-
?
dynorphin + H2O
?
show the reaction diagram
-
dynorphin A-6, A-8, A-9, A-10, A-13 and A-17
-
-
?
dynorphin(1-9) + H2O
?
show the reaction diagram
-
-
-
-
?
enkephalin + H2O
?
show the reaction diagram
-
-
-
-
?
enkephalin + H2O
?
show the reaction diagram
-
hydrolysis at Gly3-Phe4
-
-
?
enkephalin + H2O
?
show the reaction diagram
-
hydrolysis at Gly3-Phe4
-
-
?
enkephalin + H2O
?
show the reaction diagram
-
hydrolysis at Gly3-Phe4
-
-
?
exendin-4 + H2O
?
show the reaction diagram
-
poor substrate
-
-
?
galanin + H2O
?
show the reaction diagram
-
-
-
-
?
gamma-endorphin + H2O
?
show the reaction diagram
-
-
-
-
?
gastric inhibitor peptide + H2O
?
show the reaction diagram
-
poor substrate
-
-
?
gastrin G-17 + H2O
?
show the reaction diagram
-
-
-
-
?
gastrin G-17 + H2O
?
show the reaction diagram
-
cleavage at four sites, Trp4-Leu5, Ala11-Tyr12, Gly13-Trp14 and Asp16-Phe17, sulfated and unsulfated gastrin, cleavage is faster with the sulfated peptide
-
-
?
gastrin releasing peptide-10 + H2O
?
show the reaction diagram
-
-
-
-
-
GLP-1(7-36)amide + H2O
?
show the reaction diagram
-
insulinotropic peptide hormone
-
-
?
Glucagon + H2O
?
show the reaction diagram
-
-
-
-
?
Glucagon + H2O
?
show the reaction diagram
-
-, NEP24.11 is an important mediator of the degradation of both endogenous and exogenous glucagon in vivo
-
-
?
glucagon-like peptide 1 + H2O
?
show the reaction diagram
-
-
-
-
?
glutaryl-Ala-Ala-Phe-2-naphthylamide + H2O
glutaryl-Ala-Ala + Phe-2-naphthylamide
show the reaction diagram
-
-
-
?
glutaryl-Ala-Ala-Phe-4-methoxy-2-naphthylamide + H2O
glutaryl-Ala-Ala + Phe-4-methoxy-2-naphthylamide
show the reaction diagram
-
-
-
?
glutaryl-Ala-Ala-Phe-4-methoxy-2-naphthylamine + H2O
?
show the reaction diagram
-
-
-
-
?
glutaryl-Gly-Gly-Phe-2-naphthylamide + H2O
glutaryl-Gly-Gly + Phe-2-naphthylamide
show the reaction diagram
-
-
-
?
glutaryl-Gly-Gly-Phe-2-naphthylamide + H2O
glutaryl-Gly-Gly-Phe + 2-naphthylamine
show the reaction diagram
-
-
-
-
?
Gly-Trp-Gly + H2O
?
show the reaction diagram
-
-
-
-
?
haemoglobin + H2O
?
show the reaction diagram
-
-
-
-
?
hippuryl-Arg-Arg-Ala-2-naphthylamide + H2O
hippuryl-Arg-Arg + Ala-2-naphthylamide
show the reaction diagram
-
-
-
-
?
hippuryl-Arg-Arg-Leu-2-naphthylamide + H2O
hippuryl-Arg-Arg + Leu-2-naphthylamide
show the reaction diagram
-
-
-
-
?
hippuryl-Arg-Arg-Leu-2-naphthylamide + H2O
hippuryl-Arg-Arg + Leu-2-naphthylamide
show the reaction diagram
-
-
-
-
?
His-Lys-Thr-Asp-Ser-Phe-Val-Gly-Leu-Met-NH2 + H2O
His-Lys-Thr-Asp-Ser + Phe-Val-Gly + Leu-Met-NH2
show the reaction diagram
-
-
-
-
?
His-Lys-Thr-Asp-Ser-Phe-Val-Gly-Leu-Met-NH2 + H2O
His-Lys-Thr-Asp-Ser + Phe-Val-Gly + Leu-Met-NH2
show the reaction diagram
-
i.e. neurokinin A, hydrolysis at two sites: Ser5-Phe6 and Gly8-Leu9
-
-
?
insulin B chain + H2O
?
show the reaction diagram
-
-
-
-
?
interleukin 1beta + H2O
?
show the reaction diagram
-
-
-
-
?
Leu-2-naphthylamide + H2O
?
show the reaction diagram
-
-
-
-
?
Leu5-enkephalin + H2O
?
show the reaction diagram
-
-
-
-
?
Leu5-enkephalin + H2O
?
show the reaction diagram
-
-
-
-
?
Leu5-enkephalin + H2O
?
show the reaction diagram
-
-
-
-
?
Leu5-enkephalin + H2O
?
show the reaction diagram
-
-
-
-
?
Leu5-enkephalin-Arg6 + H2O
?
show the reaction diagram
-
-
-
-
?
Leu5-enkephalinamide + H2O
?
show the reaction diagram
-
-
-
-
?
Leu5-enkephalinamide + H2O
?
show the reaction diagram
-
-
-
-
-
Luliberin + H2O
?
show the reaction diagram
-
poor substrate
-
-
?
Luteinizing hormone-releasing hormone + H2O
?
show the reaction diagram
-
-
-
-
?
Luteinizing hormone-releasing hormone + H2O
?
show the reaction diagram
-
-
-
-
?
Luteinizing hormone-releasing hormone + H2O
?
show the reaction diagram
-
-
-
-
?
Luteinizing hormone-releasing hormone + H2O
?
show the reaction diagram
-
-
-
-
?
Met-enkephalin-Arg6-Gly7-Leu + H2O
?
show the reaction diagram
-
-
-
-
?
Met-Leu-Phe + H2O
?
show the reaction diagram
-
chemotactic peptide
-
-
?
Met5-enkephalin-Arg6 + H2O
?
show the reaction diagram
-
-
-
-
?
Met5-enkephalin-Arg6-Phe7 + H2O
?
show the reaction diagram
-
-
-
-
?
Met5-enkephalin-Arg6-Phe7 + H2O
?
show the reaction diagram
-
-
-
-
?
N-acetyl-Gly-Trp-Gly + H2O
N-acetyl-Gly + Trp-Gly
show the reaction diagram
-
-
-
-
?
N-dansyl-Ala-Gly-D-(4-nitro-Phe)-Gly + H2O
?
show the reaction diagram
-
-
-
-
?
N-dansyl-D-Ala-Gly-p-nitrophenyl-Ala-Gly + H2O
?
show the reaction diagram
-
-
-
-
?
N-formyl-L-Met-Leu-Phe + H2O
?
show the reaction diagram
-
the enzyme may play an important role in modulating chemotactic response by cleavage of the chemotactic substance N-formyl-Met-Leu-Phe
-
-
-
N-Formyl-Met-Leu-Phe + H2O
N-Formyl-Met + Leu-Phe
show the reaction diagram
-
-
-
?
Na,K-ATPase alpha subunit + H2O
?
show the reaction diagram
-
-
-
-
?
Nalpha-benzoyl-Gly-Arg-Arg-Ala-2-naphthylamide + H2O
Nalpha-benzoyl-Gly-Arg-Arg + Ala-2-naphthylamide
show the reaction diagram
-
-
-
?
Nalpha-benzoyl-Gly-Arg-Arg-Leu-2-naphthylamide + H2O
Nalpha-benzoyl-Gly-Arg-Arg + Leu-2-naphthylamide
show the reaction diagram
-
-
-
?
Nalpha-benzoyl-Gly-Arg-Arg-Phe-2-naphthylamide + H2O
Nalpha-benzoyl-Gly-Arg-Arg + Phe-2-naphthylamide
show the reaction diagram
-
-
-
?
Nalpha-benzoyl-Gly-Arg-Leu-2-naphthylamide + H2O
Nalpha-benzoyl-Gly-Arg + Leu-2-naphthylamide
show the reaction diagram
-
-
-
?
Nalpha-benzoyl-Gly-Gly-Arg-Leu-2-naphthylamide + H2O
Nalpha-benzoyl-Gly-Gly-Arg + Leu-2-naphthylamide
show the reaction diagram
-
-
-
?
Nalpha-benzoyl-Gly-Lys-Arg-Arg-Leu-2-naphthylamide + H2O
Nalpha-benzoyl-Gly-Lys-Arg-Arg + Leu-2-naphthylamide
show the reaction diagram
-
-
-
?
Nalpha-benzoyl-Gly-Lys-Lys-Arg-Arg-Leu-2-naphthylamide + H2O
Nalpha-benzoyl-Gly-Lys-Lys-Arg-Arg + Leu-2-naphthylamide
show the reaction diagram
-
-
-
?
neurokinin B + H2O
?
show the reaction diagram
-
-
-
-
?
neuropeptide Y + H2O
truncated neuropeptide Y + C-terminal fragments of neuropeptide Y
show the reaction diagram
-
-
neuropeptide Y 21-36 and 31-36 are the most abundant fragments generated in vivo
-
?
neurotensin + H2O
?
show the reaction diagram
-
-
-
-
?
neurotensin + H2O
?
show the reaction diagram
-
-
-
-
?
neurotensin + H2O
?
show the reaction diagram
-
-
-
-
?
neurotensin + H2O
?
show the reaction diagram
-
-
-
-
?
neurotensin + H2O
?
show the reaction diagram
-
cleaves at Pro10-Tyr11 and Tyr11-Ile12
-
-
?
oxytocin + H2O
?
show the reaction diagram
-
-
-
-
?
oxytocin + H2O
?
show the reaction diagram
-
-
-
-
?
oxytocin + H2O
?
show the reaction diagram
-
-
-
-
?
pBNP-26 + H2O
?
show the reaction diagram
-
cleaved at several sites
-
-
?
physalaemin + H2O
?
show the reaction diagram
-
-
-
-
?
physalaemin + H2O
?
show the reaction diagram
-
-
-
-
?
physalaemin + H2O
?
show the reaction diagram
-
-
-
-
?
pyroglutamyl-Leu-Asn-Phe-Thr-Pro-Asn-Trp-Gly-Thr-NH2 + H2O
pyroglutamyl-Leu-Asn + Phe-Thr-Pro-ASn-Trp-Gly-Thr-NH2
show the reaction diagram
-
-
-
?
pyroglutamyl-Leu-Asn-Phe-Thr-Pro-Asn-Trp-Gly-Thr-NH2 + H2O
pyroglutamyl-Leu-Asn + Phe-Thr-Pro-ASn-Trp-Gly-Thr-NH2
show the reaction diagram
-
-
-
?
pyroglutamyl-Leu-Asn-Phe-Thr-Pro-Asn-Trp-Gly-Thr-NH2 + H2O
pyroglutamyl-Leu-Asn + Phe-Thr-Pro-ASn-Trp-Gly-Thr-NH2
show the reaction diagram
-
-
-
?
Secretin + H2O
?
show the reaction diagram
-
-
-
-
?
striatal natriuretic factor + H2O
?
show the reaction diagram
-
-
-
-
?
Substance P + H2O
?
show the reaction diagram
-
-
-
-
-
Substance P + H2O
?
show the reaction diagram
-
-
-
-
-
Substance P + H2O
?
show the reaction diagram
-
-
-
-
-
Substance P + H2O
?
show the reaction diagram
-
-
-
-
-
Substance P + H2O
?
show the reaction diagram
-
cleaves at Gln6-Phe7, Phe7-Phe8, and Gly9-Leu10
-
-
?
Substance P + H2O
?
show the reaction diagram
-, Q9I7I4
85.8% degradation
-
-
?
succinyl-Ala-Ala-Phe-4-methylcoumarin 7-amide + H2O
succinyl-Ala-Ala + Phe-4-methylcoumarin 7-amide
show the reaction diagram
-
-
-
?
succinyl-Ala-Ala-Phe-4-methylcoumarin 7-amide + H2O
succinyl-Ala-Ala + Phe-4-methylcoumarin 7-amide
show the reaction diagram
-
-
-
-
?
succinyl-Ala-Ala-Phe-4-methylcoumarin 7-amide + H2O
succinyl-Ala-Ala + Phe-4-methylcoumarin 7-amide
show the reaction diagram
-
-
-
?
succinyl-Ala-Ala-Phe-4-methylcoumarin 7-amide + H2O
succinyl-Ala-Ala + Phe-4-methylcoumarin 7-amide
show the reaction diagram
-
-
-
-
?
succinyl-Ala-Ala-Phe-4-methylcoumarin 7-amide + H2O
succinyl-Ala-Ala + Phe-4-methylcoumarin 7-amide
show the reaction diagram
-
-
-
?
succinyl-Ala-Ala-Phe-7-amido-4-methylcoumarin + H2O
?
show the reaction diagram
-
-
-
-
?
succinyl-Ala-Ala-Phe-7-amido-4-methylcoumarin + H2O
?
show the reaction diagram
-
-
-
-
?
succinyl-Ala-Ala-Phe-p-nitroanilide + H2O
?
show the reaction diagram
-
-
-
-
?
succinyl-Arg-Arg-Leu-2-naphthylamide + H2O
succinyl-Arg-Arg + Leu-2-naphthylamide
show the reaction diagram
-
-
-
?
succinyl-Arg-Pro-Phe-His-Leu-Leu-Val-Tyr-7-amido-4-methylcoumarin + H2O
?
show the reaction diagram
-
-
-
-
?
tachykinin + H2O
?
show the reaction diagram
-, Q9I7I4
27.8% degradation
-
-
?
Tyr-D-Ala-Gly-Phe-Leu + H2O
Tyr-D-Ala-Gly + Phe-Leu
show the reaction diagram
-
-
-
?
Tyr-D-Ala-Gly-Phe-Met + H2O
Tyr-D-Ala-Gly + Phe-Met
show the reaction diagram
-
-
-
?
Tyr-D-Ala-Gly-Phe-Met + H2O
Tyr-D-Ala-Gly + Phe-Met
show the reaction diagram
-
-
-
-
?
Tyr-D-Ala-Gly-Phe-Met-NH2 + H2O
Tyr-D-Ala-Gly + Phe-Met-NH2
show the reaction diagram
-
-
-
-
?
Tyr-D-Ala-Gly-Phe-Met-NH2 + H2O
Tyr-D-Ala-Gly + Phe-Met-NH2
show the reaction diagram
-
-
-
?
Tyr-D-Ala-Gly-Phe-Met-NH2 + H2O
Tyr-D-Ala-Gly + Phe-Met-NH2
show the reaction diagram
-
-
-
-
-
Tyr-Gly-Gly-Phe-Met + H2O
Tyr-Gly-Gly + Phe-Met
show the reaction diagram
-
i.e. methionine enkephalin
-
-
?
Tyr-Gly-Gly-Phe-Met + H2O
Tyr-Gly-Gly + Phe-Met
show the reaction diagram
-
i.e. methionine enkephalin
-
-
?
Tyr-Gly-Gly-Phe-Met + H2O
Tyr-Gly-Gly + Phe-Met
show the reaction diagram
-
i.e. methionine enkephalin
-
-
?
Tyr-Gly-Gly-Phe-Met + H2O
Tyr-Gly-Gly + Phe-Met
show the reaction diagram
-
i.e. methionine enkephalin
-
-
?
Vasoactive intestinal peptide + H2O
?
show the reaction diagram
-
-
-
-
?
Met5-enkephalin-Arg6-Phe7 + H2O
?
show the reaction diagram
-
-
-
-
?
additional information
?
-
-
-
-
-
-
additional information
?
-
-
-
-
-
-
additional information
?
-
-
could play an important role in the hydrolysis of neuropeptides
-
-
-
additional information
?
-
-
physiological role in metabolism of insect peptides at the synapse
-
-
-
additional information
?
-
-
the enzyme may play an important role as regulator of plasma-derived peptides in the nephron
-
-
-
additional information
?
-
-
elevation of the enzyme activity in serum from underground coal miners exposed to chronic inhalation of coal mine dust particles. The enzyme reflects the chronic pulmonary inflammatory state induced by coalmine dust exposure, and so may be a marker of lung injury
-
-
-
additional information
?
-
-
the enzyme is involved in the processing of other peptide hormones
-
-
-
additional information
?
-
-
the enzyme is responsible for the difference in metabolism of sulfated and unsulfated gastrin in human circulation
-
-
-
additional information
?
-
-
the enzyme is the major inactivator of enkephalin in brain
-
-
-
additional information
?
-
-
the enzyme may participate in the regulation of blood pressure and water and sodium excretion through inactivation of kinins
-
-
-
additional information
?
-
-
catabolism of atrial and brain natriuretic peptide is independent of neutral endopeptidase. One or more other peptidase degrade atrial natriuretic peptide or brain natriuretic peptide in the heart, lungs and kidney
-
-
-
additional information
?
-
-
in sepsis, the local concentration and action of adrenomedullin in tissue may be differentially regulated by NEP
-
-
-
additional information
?
-
-
induction of neutral endopeptidase (NEP) activity of SK-N-SH cells by natural compounds from green tea. Caffeine leads to an increase in specific cellular neutral endopeptidase activity more than theophylline, theobromine or theanine. The combination of epigallocatechin and epigallocatechingallate with caffeine, theobromine or theophylline induces cellular neutral endopeptidase activity. The enhancement of cellular neutral endopeptidase activity by green tea extract and its natural products might be correlated with an elevated level of intracellular cyclic adenosine monophosphate
-
-
-
additional information
?
-
-
NEP-1 plays an important role in the regulation of nematode locomation. NEP-1 is a central component that controls the neuronal innervation of pharyngeal pumping in Caenorhabditis elegans
-
-
-
additional information
?
-
-
neutral endopeptidase 24.11/CD10 suppresses the progression of ovarian carcinomas
-
-
-
additional information
?
-
-
neutral endopeptidase inhibition has natriuretic and aquaretic actions in cirrhosis without any effect on blood pressure and kidney perfusion due to a significant overexpression of thgis enzyme in renal cortex
-
-
-
additional information
?
-
-
nicastrin controls neprilysin at a transcriptional level by contributing to the production of the beta-amyloid precursor protein intracellular domain with the gamma-secretase complex
-
-
-
additional information
?
-
-
no activity with angiotensin (1-7)
-
-
-
additional information
?
-
-
hydrolysis of polypeptides between hydrophobic residues
-
-
-
additional information
?
-
-
a quenched fluorogenic peptide substrate containing the first seven residues of the Abeta peptide plus a C-terminal Cysteine residue is synthesized to detect neprilysin activity. A fluorophore is attached to the C-terminal Cysteine and its fluorescence is quenched by a quencher linked to the N-terminus of the peptide
-
-
?
NATURAL SUBSTRATES
NATURAL PRODUCTS
REACTION DIAGRAM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
(Substrate)
LITERATURE
(Substrate)
COMMENTARY
(Product)
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
Atrial natriuretic factor + H2O
?
show the reaction diagram
-
dominant enzyme in the hydrolysis of atrial natriuretic factor
-
-
-
N-formyl-L-Met-Leu-Phe + H2O
?
show the reaction diagram
-
the enzyme may play an important role in modulating chemotactic response by cleavage of the chemotactic substance N-formyl-Met-Leu-Phe
-
-
-
Na,K-ATPase alpha subunit + H2O
?
show the reaction diagram
-
-
-
-
?
neuropeptide Y + H2O
truncated neuropeptide Y + C-terminal fragments of neuropeptide Y
show the reaction diagram
-
-
neuropeptide Y 21-36 and 31-36 are the most abundant fragments generated in vivo
-
?
Glucagon + H2O
?
show the reaction diagram
-
NEP24.11 is an important mediator of the degradation of both endogenous and exogenous glucagon in vivo
-
-
?
additional information
?
-
-
-
-
-
-
additional information
?
-
-
-
-
-
-
additional information
?
-
-
could play an important role in the hydrolysis of neuropeptides
-
-
-
additional information
?
-
-
physiological role in metabolism of insect peptides at the synapse
-
-
-
additional information
?
-
-
the enzyme may play an important role as regulator of plasma-derived peptides in the nephron
-
-
-
additional information
?
-
-
elevation of the enzyme activity in serum from underground coal miners exposed to chronic inhalation of coal mine dust particles. The enzyme reflects the chronic pulmonary inflammatory state induced by coalmine dust exposure, and so may be a marker of lung injury
-
-
-
additional information
?
-
-
the enzyme is involved in the processing of other peptide hormones
-
-
-
additional information
?
-
-
the enzyme is responsible for the difference in metabolism of sulfated and unsulfated gastrin in human circulation
-
-
-
additional information
?
-
-
the enzyme is the major inactivator of enkephalin in brain
-
-
-
additional information
?
-
-
the enzyme may participate in the regulation of blood pressure and water and sodium excretion through inactivation of kinins
-
-
-
additional information
?
-
-
catabolism of atrial and brain natriuretic peptide is independent of neutral endopeptidase. One or more other peptidase degrade atrial natriuretic peptide or brain natriuretic peptide in the heart, lungs and kidney
-
-
-
additional information
?
-
-
in sepsis, the local concentration and action of adrenomedullin in tissue may be differentially regulated by NEP
-
-
-
additional information
?
-
-
induction of neutral endopeptidase (NEP) activity of SK-N-SH cells by natural compounds from green tea. Caffeine leads to an increase in specific cellular neutral endopeptidase activity more than theophylline, theobromine or theanine. The combination of epigallocatechin and epigallocatechingallate with caffeine, theobromine or theophylline induces cellular neutral endopeptidase activity. The enhancement of cellular neutral endopeptidase activity by green tea extract and its natural products might be correlated with an elevated level of intracellular cyclic adenosine monophosphate
-
-
-
additional information
?
-
-
NEP-1 plays an important role in the regulation of nematode locomation. NEP-1 is a central component that controls the neuronal innervation of pharyngeal pumping in Caenorhabditis elegans
-
-
-
additional information
?
-
-
neutral endopeptidase 24.11/CD10 suppresses the progression of ovarian carcinomas
-
-
-
additional information
?
-
-
neutral endopeptidase inhibition has natriuretic and aquaretic actions in cirrhosis without any effect on blood pressure and kidney perfusion due to a significant overexpression of thgis enzyme in renal cortex
-
-
-
additional information
?
-
-
nicastrin controls neprilysin at a transcriptional level by contributing to the production of the beta-amyloid precursor protein intracellular domain with the gamma-secretase complex
-
-
-
METALS and IONS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
Zinc
-
zinc-containing metalloenzyme
Zinc
-
kidney enzyme contains 1 Zn atom per subunit
Zinc
-
-
Zinc
-
zinc-containing metalloenzyme
Cu2+
-
enzymatic activity is decreased in a dose-and time-dependent manner
additional information
-
metalloproteinase
additional information
-
-
INHIBITORS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
(2(R,S)-2-sulfanyl-2-benzyl)acetyl-Ala-Pro
-
-
(2(R,S)-2-sulfanyl-2-benzyl)acetyl-Leu-Tyr
-
-
(2(R,S)-2-sulfanyl-2-benzyl)acetyl-Phe-Ala
-
-
(2(R,S)-2-sulfanyl-2-benzyl)acetyl-Phe-Tyr
-
-
(2(R,S)-2-sulfanyl-2-isopropyl)acetyl-Ile-Tyr
-
-
(2R)-2-([1-[(5-ethyl-1,3,4-thiadiazol-2-yl)carbamoyl]cyclopentyl]methyl)pentanoic acid
-
-
(2R)-2-[(1-[[(1S)-1-carboxy-2-(3-phenyl-1,2,4-oxadiazol-5-yl)ethyl]carbamoyl]cyclopentyl)methyl]-5-oxopentanoic acid
-
-
(2R)-2-[(1-[[(1S)-1-carboxy-2-(4-ethyl-1,3-oxazol-2-yl)ethyl]carbamoyl]cyclopentyl)methyl]pentanoic acid
-
-
(2R)-2-[(1-[[(1S)-1-carboxy-2-(4-phenyl-1,3-oxazol-2-yl)ethyl]carbamoyl]cyclopentyl)methyl]-5-oxopentanoic acid
-
-
(2R)-2-[(1-[[(1S)-1-carboxy-2-(4-phenyl-1,3-oxazol-2-yl)ethyl]carbamoyl]cyclopentyl)methyl]pentanoic acid
-
-
(2R)-2-[(1-[[(1S)-1-carboxy-2-(5-phenyl-1,3,4-oxadiazol-2-yl)ethyl]carbamoyl]cyclopentyl)methyl]-5-oxopentanoic acid
-
-
(2R)-2-[(1-[[(1S)-1-carboxy-2-(5-phenyl-1,3-oxazol-2-yl)ethyl]carbamoyl]cyclopentyl)methyl]-5-oxopentanoic acid
-
-
(2R)-2-[(1-[[(1S)-1-carboxy-2-(5-phenyl-1,3-oxazol-2-yl)ethyl]carbamoyl]cyclopentyl)methyl]pentanoic acid
-
-
(2R)-2-[[1-([(1S)-1-carboxy-2-[4-(2-methylpropyl)-1,3-oxazol-2-yl]ethyl]carbamoyl)cyclopentyl]methyl]pentanoic acid
-
-
(2R)-2-[[1-([(1S)-1-carboxy-2-[5-(4-chlorophenyl)-1,3-oxazol-2-yl]ethyl]carbamoyl)cyclopentyl]methyl]-5-oxopentanoic acid
-
-
(2S)-2-[(1-[[2-(hydroxymethyl)-2,3-dihydro-1H-inden-2-yl]carbamoyl]cyclopentyl)methyl]-4-methoxybutanoic acid
-
-
(2S)-2-[(1-[[3-(4-chlorophenyl)propyl]carbamoyl]cyclopentyl)methyl]-4-methoxybutanoic acid
-
-
(2S)-2-[(1-[[3-(4-fluorophenyl)propyl]carbamoyl]cyclopentyl)methyl]-4-methoxybutanoic acid
-
-
(2S)-2-[[(2S)-1-[[(1S)-2-(biphenyl-4-yl)-1-carboxyethyl]amino]-5-methyl-1-oxohexan-2-yl]amino]-4-phenylbutanoic acid (non-preferred name)
-
-
(2S)-4-methoxy-2-([1-[(1-methyl-2-phenylethyl)carbamoyl]cyclopentyl]methyl)butanoic acid
-
-
(2S)-4-methoxy-2-[(1-[[(1R,2S)-2-(4-methoxyphenyl)cyclopropyl]carbamoyl]cyclopentyl)methyl]butanoic acid
-
-
(S)-N-[2-(phosphonomethylamino)-3-(4-biphenylyl)-propionyl]-3-aminopropionic acid
-
effects of neutral endopeptidase in acute inflammation in the lung are studied using a newly developed murine model of smoke and burn injury using NEP antagonist CGS-24592. Smoke and burn-induced lung injury and inflammation in mice pretreated with CGS-24592 is exacerbated, leading to more plasma extravasation and severe airway inflammation
1,10-phenanthroline
-
-
1,10-phenanthroline
-
-
1,10-phenanthroline
-
-
1,10-phenanthroline
-
-
2,3-Dimercaptopropan-1-ol
-
weak
2-(1-heptylcarbamoyl-cyclopentylmethyl)-4-methoxy-butyric acid tert-butyl ester
-
-
2-([1-[(1,3-benzodioxol-5-ylmethyl)carbamoyl]cyclopentyl]methyl)pentanoic acid
-
IC50: 1500 nM
2-([1-[(1-benzyl-2-hydroxyethyl)carbamoyl]cyclopentyl]methyl)pentanoic acid
-
IC50: 384 nM
2-([1-[(1-benzyl-6-oxo-1,6-dihydropyridin-3-yl)carbamoyl]cyclopentyl]methyl)pentanoic acid
-
IC50: 313 nM
2-([1-[(1-ethyl-1H-1,2,3-triazol-4-yl)carbamoyl]cyclopentyl]methyl)pentanoic acid
-
IC50: 82 nM
2-([1-[(3-ethylpyridin-2-yl)carbamoyl]cyclopentyl]methyl)pentanoic acid
-
IC50: 1710 nM
2-([1-[(4-benzylpyridin-2-yl)carbamoyl]cyclopentyl]methyl)pentanoic acid
-
IC50: 96 nM
2-([1-[(4-butylpyridin-2-yl)carbamoyl]cyclopentyl]methyl)pentanoic acid
-
IC50: 184 nM
2-([1-[(4-carbamoylcyclohexyl)carbamoyl]cyclopentyl]methyl)pentanoic acid
-
IC50: 150 nM
2-([1-[(5-benzyl-1,3,4-thiadiazol-2-yl)carbamoyl]cyclopentyl]methyl)pentanoic acid
-
IC50: 30 nM
2-([1-[(5-ethyl-1,3,4-thiadiazol-2-yl)carbamoyl]cyclopentyl]methyl)-4-phenylbutanoic acid
-
IC50: 46 nM
2-([1-[(5-ethyl-1,3,4-thiadiazol-2-yl)carbamoyl]cyclopentyl]methyl)-5-methylhexanoic acid
-
IC50: 120 nM
2-([1-[(5-ethyl-1,3,4-thiadiazol-2-yl)carbamoyl]cyclopentyl]methyl)hexanoic acid
-
IC50: 84 nM
2-([1-[(5-ethyl-1,3,4-thiadiazol-2-yl)carbamoyl]cyclopentyl]methyl)pentanoic acid
-
IC50: 60 nM
2-([1-[(5-methyl-1,3,4-thiadiazol-2-yl)carbamoyl]cyclopentyl]methyl)pentanoic acid
-
IC50: 176 nM
2-([1-[(5-phenyl-1,3,4-thiadiazol-2-yl)carbamoyl]cyclopentyl]methyl)pentanoic acid
-
IC50: 283 nM
2-([1-[(6-methoxypyridazin-3-yl)carbamoyl]cyclopentyl]methyl)pentanoic acid
-
IC50: 374 nM
2-([1-[5-(1-benzyl-6-oxo-1,6-dihydropyridin-3-yl)-1,3,4-oxadiazol-2-yl]cyclopentyl]methyl)pentanoic acid
-
IC50: 1139 nM
2-mercaptoethanol
-
-
2-mercaptoethanol
-
-
2-methoxymethyl-3-[1-(trans-2-phenyl-cyclopropylcarbamoyl)-cyclopentyl]-propionic acid tert-butyl ester
-
-
2-[(1-[[(1R)-1-phenylethyl]carbamoyl]cyclopentyl)methyl]pentanoic acid
-
IC50: 530 nM
2-[(1-[[(1R)-3-(dimethylcarbamoyl)cyclohexyl]carbamoyl]cyclopentyl)methyl]pentanoic acid
-
IC50: 297 nM
2-[(1-[[(1R,2R)-2-benzylcyclohexyl]carbamoyl]cyclopentyl)methyl]pentanoic acid
-
IC50: 195 nM
2-[(1-[[(1R,2S)-2-propylcyclohexyl]carbamoyl]cyclopentyl)methyl]pentanoic acid
-
IC50: 890 nM
2-[(1-[[(3R)-1-benzylpyrrolidin-3-yl]carbamoyl]cyclopentyl)methyl]pentanoic acid
-
IC50: 1060 nM
2-[(1-[[(3R)-1-carbamoylpyrrolidin-3-yl]carbamoyl]cyclopentyl)methyl]pentanoic acid
-
IC50: 213 nM
2-[(1-[[(5-methyl-1,3,4-thiadiazol-2-yl)methyl]carbamoyl]cyclopentyl)methyl]pentanoic acid
-
IC50: 700 nM
2-[(1-[[1-(hydroxymethyl)cyclopentyl]carbamoyl]cyclopentyl)methyl]pentanoic acid
-
IC50: 1710 nM
2-[(1-[[2-(hydroxymethyl)-2,3-dihydro-1H-inden-2-yl]carbamoyl]cyclopentyl)methyl]pentanoic acid
-
IC50: 96 nM
2-[(1-[[4-(dimethylcarbamoyl)cyclohexyl]carbamoyl]cyclopentyl)methyl]pentanoic acid
-
IC50: 370 nM
2-[(1-[[5-(2-methylpropyl)-1,3,4-thiadiazol-2-yl]carbamoyl]cyclopentyl)methyl]pentanoic acid
-
IC50: 124 nM
2-[(1-[[5-(cyclopropylmethyl)-1,3,4-thiadiazol-2-yl]carbamoyl]cyclopentyl)methyl]pentanoic acid
-
IC50: 38 nM
2-[(3-iodo-4-hydroxy)phenylmethyl]-4-N-[3-hydroxyamino-3-oxo-1(phenylmethyl)propyl]amino-4-oxobutanoic acid
-
i.e. RB104, use of the inhibitor in detecting nanogram quantities of the enzyme by inhibitor gel electrophoresis
2-[(3-iodohydroxy)phenylmethyl]-4-N-[3-hydroxyamino-3-oxo-1-phenylmethylpropyl]-amino-4-oxobutanoic acid
-
i.e. RB104, highly selective and potent inhibitor
2-[1-(2-hydroxymethyl-indan-2-ylcarbamoyl)-cyclopentylmethyl]-4-methoxy-butyric acid tert-butyl ester
-
-
2-[1-(4-butyl-pyridin-2-ylcarbamoyl)-cyclopentylmethyl]-4-methoxybutyric acid benzyl ester
-
-
2-[1-(5-ethyl-[1,3,4]thiadiazol-2-ylcarbamoyl)-cyclopentylmethyl]-pentanoic acid
-
-
2-[1-[2-(trans-4-chlorophenyl)-cyclopropylcarbamoyl]-cyclopentylmethyl]-4-methoxy-butyric acid tert-butyl ester
-
-
2-[1-[3-(4-chloro-phenyl)-propylcarbamoyl]-cyclopentylmethyl]-4-methoxy-butyric acid tert-butyl ester
-
-
2-[1-[3-(4-fluoro-phenyl)-propylcarbamoyl]-cyclopentylmethyl]-4-methoxy-butyric acid tert-butyl ester
-
-
2-[[1-(1,3,4-thiadiazol-2-ylcarbamoyl)cyclopentyl]methyl]pentanoic acid
-
IC50: 377 nM
2-[[1-(2,3-dihydro-1H-inden-2-ylcarbamoyl)cyclopentyl]methyl]pentanoic acid
-
IC50: 313 nM
2-[[1-(5-benzyl-1,3,4-oxadiazol-2-yl)cyclopentyl]methyl]pentanoic acid
-
IC50: 3100 nM
2-[[1-(pyridin-2-ylcarbamoyl)cyclopentyl]methyl]pentanoic acid
-
IC50: 1500 nM
3-[1-[(5-ethyl-1,3,4-thiadiazol-2-yl)carbamoyl]cyclopentyl]propanoic acid
-
IC50: 237 nM
3-[1-[2-(trans-4-chlorophenyl)-cyclopropylcarbamoyl]-cyclopentyl]-2-methoxymethyl-propionic acid tert-butyl ester
-
-
4-hydroxy-nonenal
-
intracellular neprilysin develops 4-hydroxy-nonenal adducts after 24 h of 4-hydroxy-nonenal treatment. 4-Hydroxy-nonenal-modified neprilysin shows decreased catalytic activity, which is associated with elevations in amyloid beta1-40 in SH-SY5Y and H4 APP695wt cells. Incubation of cells with amyloid beta1-42 also induces 4-hydroxy-nonenal adduction of neprilysin
4-methoxy-2-(1-phenethylcarbamoyl-cyclopentylmethyl)-butyric acid benzyl ester
-
-
4-methoxy-2-[1-(3-phenyl-propylcarbamoyl)-cyclopentylmethyl]-butyric acid tert-butyl ester
-
-
4-methoxy-2-[1-(trans-2-pentyl-cyclopropylcarbamoyl)-cyclopentylmethyl]-butyric acid tert-butyl ester
-
-
4-methoxy-2-[1-(trans-2-phenyl-cyclopropylcarbamoyl)-cyclopentylmethyl]-butyric acid tert-butyl ester
-
-
4-methoxy-2-[1-[(trans-2-(4-fluorophenyl)-cyclopropylcarbamoyl)]-cyclopentylmethyl]-butyric acid tert-butyl ester
-
-
4-methoxy-2-[1-[(trans-2-(4-methoxy-phenyl)-cyclopropylcarbamoyl)]-cyclopentylmethyl]-butyric acid tert-butyl ester
-
-
4-methoxy-2-[1-[2-(4-methoxy-phenoxy)-ethylcarbamoyl]-cyclopentylmethyl]-butyric acid tert-butyl ester
-
-
4-methoxy-2-[1-[2-(4-methoxy-phenyl)-ethylcarbamoyl]-cyclopentylmethyl]-butyric acid tert-butyl ester
-
-
4-methoxy-2-[1-[3-(4-methoxy-phenyl)-propylcarbamoyl]-cyclopentylmethyl]-butyric acid tert-butyl ester
-
-
AHU-377
-
LCZ696 comprises molecular moieties of valsartan, and of the NEP inhibitor prodrug AHU377 ((2R,4S)-5-biphenyl-4-yl-5-(3-carboxy-propionylamino)-2-methyl-pentanoic acid ethyl ester) (1:1 molar ratio). Oral administration of LCZ696 causes dose-dependent increases in atrial natriuretic peptide immunoreactivity due to NEP inhibition in Sprague-Dawley rats and provides sustained, dose-dependent blood pressure reductions in hypertensive double-transgenic rats
amyloid beta
-
amyloid beta reduces global DNA methylation whilst increasing neprilysin DNA methylation and further suppressing the neprilysin expression in mRNA and protein levels. Amyloid beta induces epigenetic effects, implying that DNA methylation may be part of a vicious cycle involving the reduction in neprilysin expression along with a resultant increase in amyloid beta accumulation, and that amyloiud beta may induce global DNA hypo-methylation
-
amyloid beta
-
infusion with amyloid beta(25-35) induces decrease of somatostatin-like immunoreactive content, somatostatin mRNA levels, phosphorylated-cAMP-response element binding protein CREB content and neprilysin levels
-
amyloid beta1-42
-
incubation of cells with amyloid beta1-42 induces 4-hydroxy-nonenal adduction of neprilysin. In an apparent compensatory response, amyloid beta-treated cells show increased neprilysin mRNA and protein expression. Despite elevations in neprilysin protein, the activity is significantly lower compared with the neprilysin protein level
-
angiotensin I
-
-
Atrial natriuretic factor
-
-
-
bradykinin
-
-
Butanedione
-
-
candoxatril
-
treatment increases plasma atrial natriuretic peptide levels and leads to significantly higher levels of atrial tissue cyclic GMP as well as plasma cyclic GMP. Candoxatril suppresses the shortening of atrial effective refractory period and monophasic action potential duration in the rapid atrial pacing model
candoxatrilat
-
application restores vagal reflex bradycardia in old rats to levels similar to those in young neutral endopeptidase inhibitor-treated rats
candoxatrilat
-
-
chymostatin
-
-
cis-4-[([1-[(2S)-2-carboxy-3-(2-methoxyethoxy)propyl]cyclopentyl]carbonyl)amino]cyclohexanecarboxylic acid
-
-
diethyl dicarbonate
-
-
diisopropyl fluorophosphate
-
-
dithiothreitol
-
weak
dithiothreitol
-
-
DL-[N-(3-mercapto-2-benzylpropanoyl)]glycine
-
following neprilysin inhibition, islet amyloid deposition and beta-cell apoptosis increase by 54 and 75%, respectively
LCZ696
-
LCZ696 is a dual-acting angiotensin II-receptor and neprilysin inhibitor (ARNI) in a single molecule: angiotensin-receptor blockade via its valsartan molecular moiety, and neprilysin inhibition via its AHU377 molecular moiety. In a randomized, double-blind, placebo-controlled, active comparator study it is shown that compared with valsartan, dual-acting LCZ696 provides complementary and fully additive reduction of blood pressure
Leu5-enkephalin
-
-
Leu5-enkephalin
-
hydrolysis of succinyl-Ala-Ala-Phe-4-methylcoumarin 7-amide
MCB3937
P08473
bifunctional inhibitor of NEP and DPP-IV
MCB4241
P08473
bifunctional inhibitor of NEP and DPP-IV
Met5-enkephalin
-
-
Met5-enkephalin
-
-
N-(2-benzyl-3-sulfanylpropanoyl)glycine
-
synthetic NEP inhibitor
N-([1-[(2S)-2-carboxy-3-[[N2-(methylsulfonyl)-L-lysyl]amino]propyl]cyclopentyl]carbonyl)-L-tyrosine
-
-
N-[(2RS)-3-hydroxyaminocarbonyl-2-benzyl-1-oxopropyl]-Gly
-
-
N-[1(R,S)-carboxy-2-phenylethyl]-Phe-p-aminobenzoate
-
-
N-[5-fluoresceinyl]-N'-[6-(3-mercapto-2-benzyl-1-oxopropyl)amino-1-hexyl]thiocarbamide
-
the inhibitor is a very potent probe for detecting membrane-bound enzyme for biological studies or diagnostic applications. Particularly useful for detecting the membrane-bound enzyme by flow cytometry
N-[N-[1(5)-carboxy-3-(4-hydroxyphenyl)propyl]-(5)-phenylalanyl]-(5)-isoserine
-
-
NaCl
-
brain enzyme; lung enzyme
NaCl
-
no inhibition of the enzyme from brain and kidney
NaCl
-
brain enzyme
neurotensin
-
-
opiorphin
-
-
Pepstatin
-
-
Phenylglyoxal
-
-
phosphate
-
-
phosphoramidon
-
neprilysin inhibition potentiates substance P-mediated neutrophil oxygen radical production and may promote other inflammatory activities during magnesium deficiency. Magnesium deficiency plus treatment with phosphoramidon reduces neprilysin activity by 48%, phosphoramidon or magnesium deficiency alone only reduce its activity by 26% and 15%, respectively
phosphoramidon
-, Q9I7I4
;
phosphoramidon
-
synthetic NEP inhibitor
phosphoramidon
-
partial
phosphoramidon
-
-
phosphoramidon
-
-
puromycin
-
-
SCH48446
-
i.e. the diiodo analog of N-[N-[1(5)-carboxy-3-(4-hydroxyphenyl)propyl]-(5)-phenylalanyl]-(5)-isoserine
-
sialorphin
-
opiorphin homologue inhibits NEP
SQ 28603
-
-
Substance P
-
-
Tat peptide 5118
-
-
tert-butyl 2-([1-[(5-benzyl-1,3,4-thiadiazol-2-yl)carbamoyl]cyclopentyl]methyl)-4-methoxybutanoate
-
-
thiol
-
kidney enzyme; lung enzyme
thiol
-
lung enzyme
thiol
-
kidney enzyme
thiol
-
brain enzyme
thiol
-
intestine enzyme; kidney enzyme
thiorphan
P07861
1 mM, completely blocks neutral endopeptidase activity
thiorphan
-
plasma and lung A-type natriuretic peptide levels in rats treated with lipopolysaccharide are significantly higher than those in the control group, but are significantly decreased by thiorphan administration. Natriuretic peptide receptor-A mRNA levels do not differ significantly among the groups. Natriuretic peptide receptor-C mRNA levels in animals treated with lipopolysaccharide plus thiorphan group are significantly higher than those in the other groups
thiorphan
-, Q9I7I4
;
thiorphan
-
thiorphan eliminates proteolysis of the alpha-subunit
thiorphan
-
-
thiorphan
-
weak
valsartan
-
LCZ696 comprises molecular moieties of valsartan, and of the NEP inhibitor prodrug AHU377 ((2R,4S)-5-biphenyl-4-yl-5-(3-carboxy-propionylamino)-2-methyl-pentanoic acid ethyl ester) (1:1 molar ratio). Oral administration of healthy volunteers is associated with increases in plasma cGMP, renin concentration and activity, and angiotensin II, providing evidence for NEP inhibition and angiotensin receptor blockade
Met5-enkephalin
-
hydrolysis of succinyl-Ala-Ala-Phe-4-methylcoumarin 7-amide
additional information
-
proteins derived from the Tat protein of HIV
-
additional information
-
both staurosporine-stimulated caspase-3 activation, p53 and neprilysin expression and activity are not affected by over-expression or depletion of presenilin complex component TMP21
-
additional information
-
application of aldosterone, atrial natriuretic peptide, asymmetric dimethylarginine, and angiotensin peptides fail to cause down-regulation of renal neprilysin expression in vitro
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
androgen
-
androgens positively regulate neural expression of neprilysin in adult male rats
-
dihydrotestosterone
-
induces a time-dependent increase in neprilysin expression. Dihydrotestosterone also significantly decreases levels of amyloid beta in androgen receptor-expressing cells transfected with amyloid precursor protein, but does not affect levels of either full-length or non-amyloidogenic, soluble amyloid precursor protein. The dihydrotestosterone-induced decrease of amyloid beta is blocked by pharmacological inhibition of neprilysin. The dihydrotestosterone-mediated increase in neprilysin expression and decrease in amyloid beta levels are not observed in rat pheochromocytoma cell 12 lacking androgen receptor and blocked in androgen receptor-expressing cells by the antagonists, cyproterone acetate and flutamide
Estrogen
-
estrogen stimulates degradation of beta-amyloid peptide by up-regulating neprilysin
minocycline
-
minocycline abrogates the amyloid beta(25-35)-induced decrease of somatostatin-like immunoreactive content, somatostatin mRNA levels, phosphorylated-cAMP-response element binding protein CREB content and neprilysin levels. Minocycline alone enhances these targets
additional information
-
both staurosporine-stimulated caspase-3 activation, p53 and neprilysin expression and activity are not affected by over-expression or depletion of presenilin complex component TMP21
-
KM VALUE [mM]
KM VALUE [mM] Maximum
SUBSTRATE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
0.0687
-
2-aminobenzoyl-ARFK-2,4-dinitrophenyl ester
-
-
0.0178
-
2-aminobenzoyl-DRFK-2,4-dinitrophenyl ester
-
-
0.0097
-
2-aminobenzoyl-FRFK-2,4-dinitrophenyl ester
-
-
0.0161
-
2-aminobenzoyl-HRFK-2,4-dinitrophenyl ester
-
-
0.0093
-
2-aminobenzoyl-IRFK-2,4-dinitrophenyl ester
-
-
0.0528
-
2-aminobenzoyl-KRFK-2,4-dinitrophenyl ester
-
-
0.003
-
2-aminobenzoyl-LRFK-2,4-dinitrophenyl ester
-
-
0.0214
-
2-aminobenzoyl-NRFK-2,4-dinitrophenyl ester
-
-
0.0117
-
2-aminobenzoyl-RAFK-2,4-dinitrophenyl ester
-
-
0.0028
-
2-aminobenzoyl-RDFK-2,4-dinitrophenyl ester
-
-
0.0043
-
2-aminobenzoyl-REFK-2,4-dinitrophenyl ester
-
-
0.054
-
2-aminobenzoyl-rGF-N-(2,4-dinitrophenyl)ethylenediamine
-
-
0.0259
-
2-aminobenzoyl-RGFK-2,4-dinitrophenyl amide
-
-
0.014
-
2-aminobenzoyl-RGFK-2,4-dinitrophenyl ester
-
-
0.0273
-
2-aminobenzoyl-rGL-N-(2,4-dinitrophenyl)ethylenediamine
-
-
0.0089
-
2-aminobenzoyl-RHFK-2,4-dinitrophenyl ester
-
-
0.9981
-
2-aminobenzoyl-RKFK-2,4-dinitrophenyl ester
-
-
0.0024
-
2-aminobenzoyl-RNFK-2,4-dinitrophenyl ester
-
-
0.0075
-
2-aminobenzoyl-RPFK-2,4-dinitrophenyl ester
-
-
0.0121
-
2-aminobenzoyl-RQFK-2,4-dinitrophenyl ester
-
-
0.035
-
2-aminobenzoyl-RRFK-2,4-dinitrophenyl amide
-
-
0.0089
-
2-aminobenzoyl-RRFK-2,4-dinitrophenyl ester
-
-
0.028
-
2-aminobenzoyl-rRL-N-(2,4-dinitrophenyl)ethylenediamine
-
-
0.0084
-
2-aminobenzoyl-RSFK-2,4-dinitrophenyl ester
-
-
0.0259
-
2-aminobenzoyl-rSL-N-(2,4-dinitrophenyl)ethylenediamine
-
-
0.0108
-
2-aminobenzoyl-RTFK-2,4-dinitrophenyl ester
-
-
0.0081
-
2-aminobenzoyl-SRFK-2,4-dinitrophenyl ester
-
-
0.0095
-
2-aminobenzoyl-TRFK-2,4-dinitrophenyl ester
-
-
0.0109
-
2-aminobenzoyl-VRFK-2,4-dinitrophenyl ester
-
-
0.051
-
2-aminobenzoyl-WRFK-2,4-dinitrophenyl ester
-
-
0.0583
-
2-aminobenzoyl-YRFK-2,4-dinitrophenyl ester
-
-
0.0028
-
adrenocorticotropic hormone
-
-
-
0.109
-
Ala-Leu-enkephalin
-
wild type enzyme
0.135
-
alpha-neoendorphin
-
-
0.0004
-
angiotensin I
-
-
0.036
-
angiotensin I
-
-
34.1
-
angiotensin I
-
37C, pH 7.4
0.179
-
angiotensin II
-
37C, pH 7.4
0.1114
-
angiotensin(1-9)
-
37C, pH 7.4
0.13
-
benzoyl-Gly-Gly-Leu-p-nitroanilide
-
-
0.25
-
benzyloxycarbonyl-Ala-Gly-Leu-Ala
-
-
0.00654
-
beta-endorphin
-
-
-
0.005
-
bradykinin
-
-
0.092
-
bradykinin
-
-
0.092
-
bradykinin
-
-
0.092
-
bradykinin
-
-
0.12
-
bradykinin
-
-
0.162
-
bradykinin
-
-
0.296
-
cholecystokinin-8
-
-
0.07
-
D-Ala2-Leu5-enkephalin
-
enzyme from tubules
0.076
-
D-Ala2-Leu5-enkephalin
-
enzyme from glomeruli
0.088
-
D-Ala2-Leu5-enkephalin
-
-
0.104
-
D-Ala2-Leu5-enkephalin
-
-
0.24
-
D-Ala2-Leu5-enkephalin
-
mutant enzyme R102M/N542G
1.399
-
D-Ala2-Leu5-enkephalin
-
mutant enzyme N542G
2.137
-
D-Ala2-Leu5-enkephalin
-
mutant enzyme R102M/N542G
0.773
-
D-Ala2-Leu5-enkephalinamide
-
-
0.432
-
D-Ala2-Met5-enkephalinamide
-
-
0.03
-
dansyl-Gly-Trp-Gly
-
-
0.041
-
dansyl-Gly-Tyr-Gly
-
-
0.09
-
dansyl-Gly-Tyr-Gly-NH2
-
-
0.035
-
dynorphin A-10
-
-
0.01
-
dynorphin A-13
-
-
0.0082
-
dynorphin A-17
-
-
0.025
-
dynorphin A-6
-
-
0.298
-
dynorphin A-8
-
-
0.04
-
dynorphin A-9
-
-
0.119
-
dynorphin(1-9)
-
-
0.049
-
gastrin G-17
-
sulfated
0.068
-
gastrin G-17
-
unsulfated
0.59
-
glutaryl-Ala-Ala-Phe-2-naphthylamide
-
-
0.12
-
glutaryl-Ala-Ala-Phe-4-methoxy-2-naphthylamine
-
-
0.42
-
glutaryl-Ala-Ala-Phe-4-methyoxy-2-naphthylamide
-
-
-
0.0685
-
glutaryl-Gly-Gly-Phe-2-naphthylamide
-
-
0.38
-
hippuryl-Arg-Arg-Ala-2-naphthylamide
-
-
0.35
-
hippuryl-Arg-Arg-Leu-2-naphthylamide
-
-
0.133
-
His-Lys-Thr-Asp-Ser-Phe-Val-Gly-Leu-Met-NH2
-
-
0.074
-
Leu-enkephalin
-
-
0.2
-
Leu-enkephalin
-
-
0.612
-
Leu-enkephalinamide
-
-
0.086
-
Leu5-enkephalin
-
-
0.111
-
Leu5-enkephalin-Arg6
-
-
0.68
-
Leu5-enkephalinamide
-
-
0.755
-
Luteinizing hormone-releasing hormone
-
-
0.755
-
Luteinizing hormone-releasing hormone
-
-
0.022
-
Met-enkephalin
-
-
0.04
-
Met-enkephalin
-
-
0.1
-
Met-enkephalin
-
-
0.41
-
Met-enkephalinamide
-
-
0.062
-
Met5-enkephalin
-
-
0.039
-
Met5-enkephalin-Arg6
-
-
-
0.05
-
Met5-enkephalin-Arg6Phe7
-
-
-
0.0408
-
N-2-aminobenzoyl-rGV-N-(2,4-dinitrophenyl)ethylenediamine
-
-
0.3
-
Nalpha-benzoyl-Gly-Arg-Arg-Ala-2-naphthylamide
-
-
0.18
-
Nalpha-benzoyl-Gly-Arg-Arg-Leu-2-naphthylamide
-
-
0.11
-
Nalpha-benzoyl-Gly-Arg-Arg-Phe-2-naphthylamide
-
-
0.19
-
Nalpha-benzoyl-Gly-Arg-Leu-2-naphthylamide
-
-
0.11
-
Nalpha-benzoyl-Gly-Gly-Arg-Leu-2-naphthylamide
-
-
0.08
-
Nalpha-benzoyl-Gly-Lys-Arg-Arg-Leu-2-naphthylamide
-
-
0.03
-
Nalpha-benzoyl-Gly-Lys-Lys-Arg-Arg-Leu-2-naphthylamide
-
-
0.039
-
neurotensin
-
-
0.078
-
neurotensin
-
-
0.106
-
Physalaemin
-
-
0.01
-
Substance P
-
-
0.0319
-
Substance P
-
-
0.032
-
Substance P
-
-
0.032
-
Substance P
-
-
0.19
-
Substance P
-
-
0.043
-
succinyl-Ala-Ala-Phe-4-methylcoumarin 7-amide
-
enzyme from amniotic fluid
0.052
-
succinyl-Ala-Ala-Phe-4-methylcoumarin 7-amide
-
-
0.054
-
succinyl-Ala-Ala-Phe-4-methylcoumarin 7-amide
-
enzyme from cerebrospinal fluid
0.073
-
succinyl-Ala-Ala-Phe-4-methylcoumarin 7-amide
-
-
0.058
-
succinyl-Ala-Ala-Phe-AMC
-
plasma enzyme
-
0.45
-
succinyl-Arg-Arg-Leu-2-naphthylamide
-
-
0.057
-
sulfated cholecystokinin octapeptide
-
-
0.018
-
Tyr-D-Ala-Gly-Phe-Leu
-
-
0.019
-
Tyr-D-Ala-Gly-Phe-Leu
-
-
0.013
-
Tyr-D-Ala-Gly-Phe-Met
-
-
0.061
-
Tyr-D-Ala-Gly-Phe-met-NH2
-
-
0.072
-
Tyr-D-Ala-Gly-Phe-met-NH2
-
-
0.32
-
Tyr-D-Ala-Gly-Phe-met-NH2
-
-
0.008
-
Tyr-Gly-Gly-Phe-Met
-
-
0.033
-
unsulfated cholecystokinin octapeptide
-
-
0.0018
-
Vasoactive intestinal peptide
-
-
TURNOVER NUMBER [1/s]
TURNOVER NUMBER MAXIMUM[1/s]
SUBSTRATE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
1.7
-
adrenocorticotropic hormone
-
-
-
44.6
-
alpha-neoendorphin
-
-
0.0551
-
angiotensin I
-
37C, pH 7.4
40
-
angiotensin II
-
37C, pH 7.4
41.8
-
angiotensin(1-9)
-
37C, pH 7.4
0.05
-
benzoyl-Gly-Gly-Arg-Leu-2-naphthylamide
-
-
0.105
-
benzoyl-Gly-Gly-Leu-p-nitroanilide
-
-
46.4
-
benzyloxycarbonyl-Ala-Gly-Leu-Ala
-
-
26
-
beta-endorphin
-
-
-
4.3
-
bradykinin
-
-
106
-
bradykinin
-
-
19
-
D-Ala2-Leu5-enkephalin
-
enzyme from tubules
20.7
-
D-Ala2-Leu5-enkephalin
-
enzyme from glomeruli
232
-
D-Ala2-Leu5-enkephalin
-
mutant enzyme N542G
412
-
D-Ala2-Leu5-enkephalin
-
mutant enzyme R102M/N542G
1020
-
D-Ala2-Leu5-enkephalin
-
wild type enzyme
1260
-
D-Ala2-Leu5-enkephalin
-
mutant enzyme R102M
15
-
dansyl-Gly-Trp-Gly
-
-
19.1
-
dansyl-Gly-Tyr-Gly
-
-
4.13
-
dansyl-Gly-Tyr-Gly-NH2
-
-
23.8
-
dynorphin A-10
-
-
18.6
-
dynorphin A-13
-
-
25.4
-
dynorphin A-17
-
-
14
-
dynorphin A-6
-
-
19.6
-
dynorphin A-8
-
-
32.2
-
dynorphin A-9
-
-
0.767
-
gastrin G-17
-
sulfated
1.07
-
gastrin G-17
-
unsulfated
9.87
-
glutaryl-Ala-Ala-Phe-2-naphthylamide
-
-
5.28
-
glutaryl-Ala-Ala-Phe-4-methoxy-2-naphthylamide
-
-
58.2
-
glutaryl-Ala-Ala-Phe-4-methoxy-2-naphthylamine
-
-
43.7
-
glutaryl-Gly-Gly-Phe-2-naphthylamide
-
-
0.883
-
Gly-Trp-Gly
-
-
6.83
-
hippuryl-Arg-Arg-Ala-2-naphthylamide
-
-
72
-
hippuryl-Arg-Arg-Leu-2-naphthylamide
-
-
15
-
Leu-enkephalin
-
-
8.2
-
Leu-enkephalinamide
-
-
14
-
Luteinizing hormone-releasing hormone
-
-
7.8
-
Met-enkephalin
-
-
0.5
-
Met-enkephalinamide
-
-
3.63
-
N-acetyl-Gly-Trp-Gly
-
-
0.147
-
Nalpha-benzoyl-Gly-Arg-Arg-Ala-2-naphthylamide
-
-
4
-
Nalpha-benzoyl-Gly-Arg-Arg-Leu-2-naphthylamide
-
-
2
-
Nalpha-benzoyl-Gly-Arg-Arg-Phe-2-naphthylamide
-
-
0.0483
-
Nalpha-benzoyl-Gly-Arg-Leu-2-naphthylamide
-
-
1.82
-
Nalpha-benzoyl-Gly-Lys-Arg-Arg-Leu-2-naphthylamide
-
-
0.383
-
Nalpha-benzoyl-Gly-Lys-Lys-Arg-Arg-Leu-2-naphthylamide
-
-
28
-
Substance P
-
-
84.3
-
Substance P
-
-
84.4
-
Substance P
-
-
6.32
-
succinyl-Arg-Arg-Leu-2-naphthylamide
-
-
31.1
-
sulfated cholecystokinin octapeptide
-
-
17.4
-
Tyr-D-Ala-Gly-Phe-Met
-
-
42
-
Tyr-D-Ala-Gly-Phe-met-NH2
-
-
21.1
-
Tyr-Gly-Gly-Phe-Met
-
-
24.6
-
unsulfated cholecystokinin octapeptide
-
-
1.8
-
Vasoactive intestinal peptide
-
-
Ki VALUE [mM]
Ki VALUE [mM] Maximum
INHIBITOR
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
0.036
-
angiotensin I
-
hydrolysis of Leu5-enkephalin
0.162
-
bradykinin
-
hydrolysis of Leu5-enkephalin
0.022
-
Met5-enkephalin
-
hydrolysis of Leu5-enkephalin
0.039
-
neurotensin
-
hydrolysis of Leu5-enkephalin
0.19
-
Substance P
-
hydrolysis of Leu5-enkephalin
0.44
-
Tat peptide 5118
-
neprilysin + 20 microg/ml peptide 5118
1.08
-
Tat peptide 5118
-
preincubated neprilysin with 20 microg/ml peptide 5118 and then diluted 10fold into the assay
1.13
-
Tat peptide 5118
-
neprilysin + 0.2 microg/ml peptide 5118
1.24
-
Tat peptide 5118
-
neprilysin inhibition by Tat peptide 5118
0.000004
-
thiorphan
P08473
-
0.00191
-
thiorphan
-
-
IC50 VALUE [mM]
IC50 VALUE [mM] Maximum
INHIBITOR
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
0.0000013
-
(2(R,S)-2-sulfanyl-2-benzyl)acetyl-Ala-Pro
-
-
0.0000022
-
(2(R,S)-2-sulfanyl-2-benzyl)acetyl-Leu-Tyr
-
-
0.0000023
-
(2(R,S)-2-sulfanyl-2-benzyl)acetyl-Phe-Ala
-
-
0.0000029
-
(2(R,S)-2-sulfanyl-2-benzyl)acetyl-Phe-Tyr
-
-
0.0000014
-
(2(R,S)-2-sulfanyl-2-isopropyl)acetyl-Ile-Tyr
-
-
0.00000237
-
(2R)-2-([1-[(5-ethyl-1,3,4-thiadiazol-2-yl)carbamoyl]cyclopentyl]methyl)pentanoic acid
-
-
0.0000019
-
(2R)-2-[(1-[[(1S)-1-carboxy-2-(3-phenyl-1,2,4-oxadiazol-5-yl)ethyl]carbamoyl]cyclopentyl)methyl]-5-oxopentanoic acid
-
pH and temperature not specified in the publication
0.000022
-
(2R)-2-[(1-[[(1S)-1-carboxy-2-(4-ethyl-1,3-oxazol-2-yl)ethyl]carbamoyl]cyclopentyl)methyl]pentanoic acid
-
pH and temperature not specified in the publication
0.0000048
-
(2R)-2-[(1-[[(1S)-1-carboxy-2-(4-phenyl-1,3-oxazol-2-yl)ethyl]carbamoyl]cyclopentyl)methyl]-5-oxopentanoic acid
-
pH and temperature not specified in the publication
0.000007
-
(2R)-2-[(1-[[(1S)-1-carboxy-2-(4-phenyl-1,3-oxazol-2-yl)ethyl]carbamoyl]cyclopentyl)methyl]pentanoic acid
-
pH and temperature not specified in the publication
0.000006
-
(2R)-2-[(1-[[(1S)-1-carboxy-2-(5-phenyl-1,3,4-oxadiazol-2-yl)ethyl]carbamoyl]cyclopentyl)methyl]-5-oxopentanoic acid
-
pH and temperature not specified in the publication
0.0000003
-
(2R)-2-[(1-[[(1S)-1-carboxy-2-(5-phenyl-1,3-oxazol-2-yl)ethyl]carbamoyl]cyclopentyl)methyl]-5-oxopentanoic acid
-
pH and temperature not specified in the publication
0.0000006
-
(2R)-2-[(1-[[(1S)-1-carboxy-2-(5-phenyl-1,3-oxazol-2-yl)ethyl]carbamoyl]cyclopentyl)methyl]pentanoic acid
-
pH and temperature not specified in the publication
0.00002
-
(2R)-2-[[1-([(1S)-1-carboxy-2-[4-(2-methylpropyl)-1,3-oxazol-2-yl]ethyl]carbamoyl)cyclopentyl]methyl]pentanoic acid
-
pH and temperature not specified in the publication
0.0000003
-
(2R)-2-[[1-([(1S)-1-carboxy-2-[5-(4-chlorophenyl)-1,3-oxazol-2-yl]ethyl]carbamoyl)cyclopentyl]methyl]-5-oxopentanoic acid
-
pH and temperature not specified in the publication
0.000005
-
(2R)-2-[[1-([(1S)-1-carboxy-2-[5-(4-chlorophenyl)-1,3-oxazol-2-yl]ethyl]carbamoyl)cyclopentyl]methyl]-5-oxopentanoic acid
-
pH and temperature not specified in the publication
0.00000054
-
(2S)-2-[(1-[[2-(hydroxymethyl)-2,3-dihydro-1H-inden-2-yl]carbamoyl]cyclopentyl)methyl]-4-methoxybutanoic acid
-
-
0.000000009
-
(2S)-2-[(1-[[3-(4-chlorophenyl)propyl]carbamoyl]cyclopentyl)methyl]-4-methoxybutanoic acid
-
-
0.0000002
-
(2S)-2-[(1-[[3-(4-fluorophenyl)propyl]carbamoyl]cyclopentyl)methyl]-4-methoxybutanoic acid
-
-
0.000028
-
(2S)-2-[[(2S)-1-[[(1S)-2-(biphenyl-4-yl)-1-carboxyethyl]amino]-5-methyl-1-oxohexan-2-yl]amino]-4-phenylbutanoic acid (non-preferred name)
-
pH and temperature not specified in the publication
0.0000426
-
(2S)-4-methoxy-2-([1-[(1-methyl-2-phenylethyl)carbamoyl]cyclopentyl]methyl)butanoic acid
-
-
0.0000008
-
(2S)-4-methoxy-2-[(1-[[(1R,2S)-2-(4-methoxyphenyl)cyclopropyl]carbamoyl]cyclopentyl)methyl]butanoic acid
-
-
0.0000008
-
2-(1-heptylcarbamoyl-cyclopentylmethyl)-4-methoxy-butyric acid tert-butyl ester
-
-
0.0015
-
2-([1-[(1,3-benzodioxol-5-ylmethyl)carbamoyl]cyclopentyl]methyl)pentanoic acid
-
IC50: 1500 nM
0.000384
-
2-([1-[(1-benzyl-2-hydroxyethyl)carbamoyl]cyclopentyl]methyl)pentanoic acid
-
IC50: 384 nM
0.000313
-
2-([1-[(1-benzyl-6-oxo-1,6-dihydropyridin-3-yl)carbamoyl]cyclopentyl]methyl)pentanoic acid
-
IC50: 313 nM
0.000082
-
2-([1-[(1-ethyl-1H-1,2,3-triazol-4-yl)carbamoyl]cyclopentyl]methyl)pentanoic acid
-
IC50: 82 nM
0.00171
-
2-([1-[(3-ethylpyridin-2-yl)carbamoyl]cyclopentyl]methyl)pentanoic acid
-
IC50: 1710 nM
0.000096
-
2-([1-[(4-benzylpyridin-2-yl)carbamoyl]cyclopentyl]methyl)pentanoic acid
-
IC50: 96 nM
0.000184
-
2-([1-[(4-butylpyridin-2-yl)carbamoyl]cyclopentyl]methyl)pentanoic acid
-
IC50: 184 nM
0.00015
-
2-([1-[(4-carbamoylcyclohexyl)carbamoyl]cyclopentyl]methyl)pentanoic acid
-
IC50: 150 nM
0.00003
-
2-([1-[(5-benzyl-1,3,4-thiadiazol-2-yl)carbamoyl]cyclopentyl]methyl)pentanoic acid
-
IC50: 30 nM
0.000046
-
2-([1-[(5-ethyl-1,3,4-thiadiazol-2-yl)carbamoyl]cyclopentyl]methyl)-4-phenylbutanoic acid
-
IC50: 46 nM
0.00012
-
2-([1-[(5-ethyl-1,3,4-thiadiazol-2-yl)carbamoyl]cyclopentyl]methyl)-5-methylhexanoic acid
-
IC50: 120 nM
0.000084
-
2-([1-[(5-ethyl-1,3,4-thiadiazol-2-yl)carbamoyl]cyclopentyl]methyl)hexanoic acid
-
IC50: 84 nM
0.00006
-
2-([1-[(5-ethyl-1,3,4-thiadiazol-2-yl)carbamoyl]cyclopentyl]methyl)pentanoic acid
-
IC50: 60 nM
0.000176
-
2-([1-[(5-methyl-1,3,4-thiadiazol-2-yl)carbamoyl]cyclopentyl]methyl)pentanoic acid
-
IC50: 176 nM
0.000283
-
2-([1-[(5-phenyl-1,3,4-thiadiazol-2-yl)carbamoyl]cyclopentyl]methyl)pentanoic acid
-
IC50: 283 nM
0.000374
-
2-([1-[(6-methoxypyridazin-3-yl)carbamoyl]cyclopentyl]methyl)pentanoic acid
-
IC50: 374 nM
0.001139
-
2-([1-[5-(1-benzyl-6-oxo-1,6-dihydropyridin-3-yl)-1,3,4-oxadiazol-2-yl]cyclopentyl]methyl)pentanoic acid
-
IC50: 1139 nM
0.0000065
-
2-methoxymethyl-3-[1-(trans-2-phenyl-cyclopropylcarbamoyl)-cyclopentyl]-propionic acid tert-butyl ester
-
-
0.00053
-
2-[(1-[[(1R)-1-phenylethyl]carbamoyl]cyclopentyl)methyl]pentanoic acid
-
IC50: 530 nM
0.000297
-
2-[(1-[[(1R)-3-(dimethylcarbamoyl)cyclohexyl]carbamoyl]cyclopentyl)methyl]pentanoic acid
-
IC50: 297 nM
0.000195
-
2-[(1-[[(1R,2R)-2-benzylcyclohexyl]carbamoyl]cyclopentyl)methyl]pentanoic acid
-
IC50: 195 nM
0.00089
-
2-[(1-[[(1R,2S)-2-propylcyclohexyl]carbamoyl]cyclopentyl)methyl]pentanoic acid
-
IC50: 890 nM
0.00106
-
2-[(1-[[(3R)-1-benzylpyrrolidin-3-yl]carbamoyl]cyclopentyl)methyl]pentanoic acid
-
IC50: 1060 nM
0.000213
-
2-[(1-[[(3R)-1-carbamoylpyrrolidin-3-yl]carbamoyl]cyclopentyl)methyl]pentanoic acid
-
IC50: 213 nM
0.0007
-
2-[(1-[[(5-methyl-1,3,4-thiadiazol-2-yl)methyl]carbamoyl]cyclopentyl)methyl]pentanoic acid
-
IC50: 700 nM
0.00171
-
2-[(1-[[1-(hydroxymethyl)cyclopentyl]carbamoyl]cyclopentyl)methyl]pentanoic acid
-
IC50: 1710 nM
0.000096
-
2-[(1-[[2-(hydroxymethyl)-2,3-dihydro-1H-inden-2-yl]carbamoyl]cyclopentyl)methyl]pentanoic acid
-
IC50: 96 nM
0.00037
-
2-[(1-[[4-(dimethylcarbamoyl)cyclohexyl]carbamoyl]cyclopentyl)methyl]pentanoic acid
-
IC50: 370 nM
0.000124
-
2-[(1-[[5-(2-methylpropyl)-1,3,4-thiadiazol-2-yl]carbamoyl]cyclopentyl)methyl]pentanoic acid
-
IC50: 124 nM
0.000038
-
2-[(1-[[5-(cyclopropylmethyl)-1,3,4-thiadiazol-2-yl]carbamoyl]cyclopentyl)methyl]pentanoic acid
-
IC50: 38 nM
0.0000011
-
2-[1-(2-hydroxymethyl-indan-2-ylcarbamoyl)-cyclopentylmethyl]-4-methoxy-butyric acid tert-butyl ester
-
-
0.0000017
-
2-[1-(4-butyl-pyridin-2-ylcarbamoyl)-cyclopentylmethyl]-4-methoxybutyric acid benzyl ester
-
-
0.000006
-
2-[1-(5-ethyl-[1,3,4]thiadiazol-2-ylcarbamoyl)-cyclopentylmethyl]-pentanoic acid
-
-
0.0000021
-
2-[1-[2-(trans-4-chlorophenyl)-cyclopropylcarbamoyl]-cyclopentylmethyl]-4-methoxy-butyric acid tert-butyl ester
-
-
0.0000002
-
2-[1-[3-(4-chloro-phenyl)-propylcarbamoyl]-cyclopentylmethyl]-4-methoxy-butyric acid tert-butyl ester
-
-
0.0000015
-
2-[1-[3-(4-fluoro-phenyl)-propylcarbamoyl]-cyclopentylmethyl]-4-methoxy-butyric acid tert-butyl ester
-
-
0.000377
-
2-[[1-(1,3,4-thiadiazol-2-ylcarbamoyl)cyclopentyl]methyl]pentanoic acid
-
IC50: 377 nM
0.000313
-
2-[[1-(2,3-dihydro-1H-inden-2-ylcarbamoyl)cyclopentyl]methyl]pentanoic acid
-
IC50: 313 nM
0.0031
-
2-[[1-(5-benzyl-1,3,4-oxadiazol-2-yl)cyclopentyl]methyl]pentanoic acid
-
IC50: 3100 nM
0.0015
-
2-[[1-(pyridin-2-ylcarbamoyl)cyclopentyl]methyl]pentanoic acid
-
IC50: 1500 nM
0.000237
-
3-[1-[(5-ethyl-1,3,4-thiadiazol-2-yl)carbamoyl]cyclopentyl]propanoic acid
-
IC50: 237 nM
0.000002
-
3-[1-[2-(trans-4-chlorophenyl)-cyclopropylcarbamoyl]-cyclopentyl]-2-methoxymethyl-propionic acid tert-butyl ester
-
-
0.00005
-
4-methoxy-2-(1-phenethylcarbamoyl-cyclopentylmethyl)-butyric acid benzyl ester
-
-
0.0000035
-
4-methoxy-2-[1-(3-phenyl-propylcarbamoyl)-cyclopentylmethyl]-butyric acid tert-butyl ester
-
-
0.000001
-
4-methoxy-2-[1-(trans-2-pentyl-cyclopropylcarbamoyl)-cyclopentylmethyl]-butyric acid tert-butyl ester
-
-
0.00001
-
4-methoxy-2-[1-(trans-2-phenyl-cyclopropylcarbamoyl)-cyclopentylmethyl]-butyric acid tert-butyl ester
-
-
0.000004
-
4-methoxy-2-[1-[(trans-2-(4-fluorophenyl)-cyclopropylcarbamoyl)]-cyclopentylmethyl]-butyric acid tert-butyl ester
-
-
0.0000008
-
4-methoxy-2-[1-[(trans-2-(4-methoxy-phenyl)-cyclopropylcarbamoyl)]-cyclopentylmethyl]-butyric acid tert-butyl ester
-
-
0.0000035
-
4-methoxy-2-[1-[2-(4-methoxy-phenoxy)-ethylcarbamoyl]-cyclopentylmethyl]-butyric acid tert-butyl ester
-
-
0.0000369
-
4-methoxy-2-[1-[2-(4-methoxy-phenyl)-ethylcarbamoyl]-cyclopentylmethyl]-butyric acid tert-butyl ester
-
-
0.0000002
-
4-methoxy-2-[1-[3-(4-methoxy-phenyl)-propylcarbamoyl]-cyclopentylmethyl]-butyric acid tert-butyl ester
-
-
0.0000078
-
cis-4-[([1-[(2S)-2-carboxy-3-(2-methoxyethoxy)propyl]cyclopentyl]carbonyl)amino]cyclohexanecarboxylic acid
-
pH and temperature not specified in the publication
0.00045
-
MCB3937
P08473
-
0.0006
-
MCB4241
P08473
-
0.0000006
-
N-([1-[(2S)-2-carboxy-3-[[N2-(methylsulfonyl)-L-lysyl]amino]propyl]cyclopentyl]carbonyl)-L-tyrosine
-
pH and temperature not specified in the publication
0.0000005
-
tert-butyl 2-([1-[(5-benzyl-1,3,4-thiadiazol-2-yl)carbamoyl]cyclopentyl]methyl)-4-methoxybutanoate
-
-
SPECIFIC ACTIVITY [µmol/min/mg]
SPECIFIC ACTIVITY MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
0.0000018
-
-
on human adipocyte membranes
0.000028
-
-
in hippocampus
0.00006
-
-
in olfactory tubercle-frontal cortex
0.00014
-
-
in mammillary nucleus
0.158
-
-
hydrolysis of insulin B-chain
0.203
-
-
cleavage of succinyl-Arg-Pro-Phe-His-Leu-Leu-Val-Tyr-4-methylcoumarin 7-amide
26.3
-
-
hydrolysis of D-Ala2-Leu5-enkephalin
additional information
-
-
-
pH OPTIMUM
pH MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
6
-
-
kidney enzyme
6.5
7
-
brain enzyme
6.5
-
-
kidney enzyme
7
7.5
-
kidney enzyme
7
-
-
hydrolysis of pyroglutamyl-Leu-Asn-Phe-Thr-Pro-Asn-Trp-Gly-Thr-NH2
7
-
-
kidney
7
-
-
intestine
7.3
7.8
-
hydrolysis of hippuryl-Arg-Arg-Leu-2-naphthylamide
7.4
-
-
-
7.4
-
-
assay at
7.5
-
-
assay at
9.5
-
-
hydrolysis of azocasein
pH RANGE
pH RANGE MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
4.5
8.5
-
-
6.5
8.8
-
pH 6.5: about 95% of maximal activity, pH 8.8.: about 40% of maximal activity, hydrolysis of pyroglutamyl-Leu-Asn-Phe-Thr-Pro-Asn-Trp-Gly-Thr-NH2
7
10.3
-
pH 7.0: about 40% of maximal activity, pH 10.3: about 25% of maximal activity
7
8.4
-
about 80% of maximal activity at pH 7.0 and at pH 8.4, hydrolysis of hippuryl-Arg-Arg-Leu-2-naphthylamide
TEMPERATURE OPTIMUM
TEMPERATURE OPTIMUM MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
35
-
-, Q9I7I4
assay at; assay at
37
-
-
assay at
37
-
-
assay at
37
-
-
assay at
SOURCE TISSUE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
SOURCE
-
adipocyte membrane
Manually annotated by BRENDA team
-
tissue NEP activity and its protein and mRNA expression are lower in the late phase of the septic shock compared to the early phase of the shock and the control
Manually annotated by BRENDA team
-
NEP expression is down-regulated in bovine vascular endothelial cells by physiological laminar shear, possibly via a mechanotransduction mechanism involving NADPH oxidase-induced reactive oxygen species production
Manually annotated by BRENDA team
-
estrogen regulates neprilysin activity in brain. Ovariectomy leads to a 30% decrease in neprilysin activity at 45 or 85 days, but not 21 days, post surgery
Manually annotated by BRENDA team
-
neprilysin specific activity varies across mouse strains, with the highest activities in kidney and brain of SW mice. Aging is associated with a reduction in brain neprilysin specific activity in SW strain and C57B1/6J strain. The aging- and strain-dependent differences in neprilysin specific activity may explain, at least in part, the roles that aging and background mouse strain play in differential specification of the susceptibility towards the development of cerebral Abeta amyloidosis
Manually annotated by BRENDA team
-
temporal cortex of amyloid beta(25-35)-infused and healthy rats
Manually annotated by BRENDA team
-
distribution of neprilysin is almost identical in dogs and cats, being high in the striatum, globus pallidus, and substantia nigra, but very low in the cerebral cortex. The white matter and hippocampus are negative. Neprilysin activity in the brain regions is ranked from high to low as follows: thalamus/striatum > cerebral cortex > hippocampus > white matter. Amyloid-beta deposition is first detected at 7 years of age in dogs, and both the quantity and frequency of deposition increase with age. Amyloid-beta deposition appears in the cerebral cortex and the hippocampus
Manually annotated by BRENDA team
-
distribution of neprilysin is almost identical in dogs and cats, being high in the striatum, globus pallidus, and substantia nigra, but very low in the cerebral cortex. The white matter and hippocampus are negative. Neprilysin activity in the brain regions is ranked from high to low as follows: thalamus/striatum > cerebral cortex > hippocampus > white matter. Amyloid-beta deposition is first detected at 10 years of age in cats, and both the quantity and frequency of deposition increase with age. Amyloid-beta deposition appears in the cerebral cortex and the hippocampus
Manually annotated by BRENDA team
-
NEP-like immunoreactivity is significantly reduced in Alzheimer's disease brains compared with normal brains, in the CA4 region NEP is preserved in the hippocampal formation of Alzheimer's disease brains
Manually annotated by BRENDA team
-
ethanol induces a transitory increase in NEP activities in the frontal cortex and ventral tegmental area, and in the nucleus accumbens
Manually annotated by BRENDA team
-
pial membranes associated with brain and spinal cord
Manually annotated by BRENDA team
-
in globus pallidus and substantia nigra much of the enzyme is associated with presynaptic nerve terminals originating from efferent striatal neurons
Manually annotated by BRENDA team
-
corpus striatum and globus pallidus
Manually annotated by BRENDA team
-
dura and pia mater
Manually annotated by BRENDA team
-
enzyme in sustantia nigra and globus pallidus is localized on nerve terminals originating from neurones in the caudate putamen
Manually annotated by BRENDA team
-
medulla, paracortex, cortex
Manually annotated by BRENDA team
-
striatum; synaptic membranes
Manually annotated by BRENDA team
-
highest activity in choroid plexus, substantia nigra, caudate putamen, globus pallidus, olfactory tubercle, nucleus accumbens. Moderate activity in amygdala, interpenducular nucleus, molecular layer of the cerebellum, periaqueductal gray matter, and the hippocampus
Manually annotated by BRENDA team
-
a large fraction of the enzyme is localized on intrinsic striatal neurons
Manually annotated by BRENDA team
-
low level of neprilysin. Amyloid-beta deposition appears in the cerebral cortex and the hippocampus
Manually annotated by BRENDA team
-
from articular cartilage
Manually annotated by BRENDA team
-
distribution of neprilysin is high in the striatum, globus pallidus, and substantia nigra, but very low in the cerebral cortex
Manually annotated by BRENDA team
-, Q9I7I4
expression is demonstrated during embryogenesis in pericardial cells, muscle founder cells, glia cells and male gonads. At least one isoform of NEP4 is found in every developmental stage; expression is demonstrated during embryogenesis in pericardial cells, muscle founder cells, glia cells and male gonads. At least one isoform of NEP4 is found in every developmental stage
Manually annotated by BRENDA team
-
cerebral endothelial cell culture
Manually annotated by BRENDA team
-
distribution of neprilysin is high in the striatum, globus pallidus, and substantia nigra, but very low in the cerebral cortex
Manually annotated by BRENDA team
-
both staurosporine-stimulated caspase-3 activation, p53 and neprilysin expression and activity are not affected by over-expression or depletion of presenilin complex component TMP21
Manually annotated by BRENDA team
-
amyloid-beta deposition appears in the cerebral cortex and the hippocampus
Manually annotated by BRENDA team
-
tissue NEP activity and its protein and mRNA expression are lower in the late phase of the septic shock compared to the early phase of the shock and the control
Manually annotated by BRENDA team
-
neprilysin specific activity varies across mouse strains, with the highest activities in kidney and brain of SW mice
Manually annotated by BRENDA team
-
no significant change in NEP activity and its protein and mRNA expression between late phase of the septic shock compared to the early phase of the shock and the control
Manually annotated by BRENDA team
-
renal mRNA expression and protein of neprilysin is substantially downregulated during rapid atrial pacing. Irbesartan therapy does not prevent down-regulation of neprilysin. In contrast, TGF-beta1 mRNA expression is up-regulated. Collagen and angiotensin II type 1 receptor expression are not significantly altered by rapid atrial pacing. Application of aldosterone, atrial natriuretic peptide, asymmetric dimethylarginine, and angiotensin peptides fail to cause down-regulation of renal neprilysin expression in vitro
Manually annotated by BRENDA team
-
microvillar membrane
Manually annotated by BRENDA team
-
glomeruli, tubules
Manually annotated by BRENDA team
-
tissue NEP activity and its protein and mRNA expression are lower in the late phase of the septic shock compared to the early phase of the shock and the control
Manually annotated by BRENDA team
-
high activity
Manually annotated by BRENDA team
-
tissue NEP activity and its protein and mRNA expression are lower in the late phase of the septic shock compared to the early phase of the shock and the control
Manually annotated by BRENDA team
-
in all myopathies NEP expression is directly associated with the degree of muscle fibre regeneration. In inclusion body myositis muscle, the NEP protein is also strongly accumulated in Abeta-bearing abnormal fibres. NEP plays an important role during muscle cell differentiation, possibly through the regulation
Manually annotated by BRENDA team
-
body wall musculature
Manually annotated by BRENDA team
-
two neuroblastoma cell lines differing substantially in NEP expression are compared: using chromatin immunoprecipitation it is shown that amyloid precursor protein is bound directly to the NEP promoter in high NEP-expresser (NB7) cells but not in low-expresser (SH-SY5Y) cells. The methylation status of the NEP promoter does not regulate expression in these cells, whereas the histone deacetylase inhibitors trichostatin A and valproate partly restore NEP expression and activity in SH-SY5Y cells
Manually annotated by BRENDA team
-
in neuroblastoma SH-SY5Y cells neprilysin expression is up-regulated estrogen
Manually annotated by BRENDA team
-
expression of nep-1 is limited to pharyngeal cells and a single head neuron
Manually annotated by BRENDA team
-
hippocampal
Manually annotated by BRENDA team
-
neprilysin is expressed in the neurons and axonally transported to presynaptic sites. Presynaptic neprilysin efficiently degrades amyloid-beta peptide and retards development of amyloid pathology
Manually annotated by BRENDA team
-
androgens positively regulate neural expression of neprilysin in adult male rats
Manually annotated by BRENDA team
-
chromatin immunoprecipitation analysis demonstrates amyloid precursor protein binding to tht NEP promoter in primary neurons
Manually annotated by BRENDA team
P07861
osteoblastic cell line PyMS
Manually annotated by BRENDA team
-
neutral endopeptidase 24.11/CD10 is expressed in tumor cells as well as stromal tissues
Manually annotated by BRENDA team
-
expression throughout development with highest mRNA level in embryos, 1.3 larvae and adult worms. Expression of nep-1 is limited to pharyngeal cells and a single head neuron
Manually annotated by BRENDA team
-
high activity in glandular epithelium, weak activity in stroma
Manually annotated by BRENDA team
-
present in many, but not all Schwann cell membranes
Manually annotated by BRENDA team
-
induction of neutral endopeptidase (NEP) activity of SK-N-SH cells by natural compounds from green tea. Caffeine leads to an increase in specific cellular neutral endopeptidase activity more than theophylline, theobromine or theanine. The combination of epigallocatechin and epigallocatechingallate with caffeine, theobromine or theophylline induces cellular neutral endopeptidase activity. The enhancement of cellular neutral endopeptidase activity by green tea extract and its natural products might be correlated with an elevated level of intracellular cyclic adenosine monophosphate
Manually annotated by BRENDA team
-
pial membranes associated with brain and spinal cord
Manually annotated by BRENDA team
-
distribution of neprilysin is high in the striatum, globus pallidus, and substantia nigra, but very low in the cerebral cortex
Manually annotated by BRENDA team
-
capsule, subcapsular zone, Hassall's corpuscles
Manually annotated by BRENDA team
additional information
-
no activity of CD10/neutral endopeptidase is detected in cultured, non-stimulated keratinocytes from healthy skin
Manually annotated by BRENDA team
additional information
-
in cerebrocortical blood vessels and in pyramidal neurons
Manually annotated by BRENDA team
additional information
-
the enzyme is expressed all along the differentiation pathway in B and T cell lineage
Manually annotated by BRENDA team
LOCALIZATION
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
-, Q9I7I4
isoform A is expressed as a membrane bound protein
Manually annotated by BRENDA team
-
integral membrane protein
Manually annotated by BRENDA team
-
axonal membranes, including those in synaptic junctions
Manually annotated by BRENDA team
-
integral membrane protein
Manually annotated by BRENDA team
-
plasma membrane
Manually annotated by BRENDA team
-
the enzyme possesses a single transmembrane spanning domain near the N-terminal of the molecule, the active site is located extracellularly, the N-terminal transmembrane region anchors the protein in the membranes, the majority of the protein, including the carboxy terminus is extracellular
Manually annotated by BRENDA team
-
synaptic membranes
Manually annotated by BRENDA team
-
caudate and synaptic membranes
Manually annotated by BRENDA team
-
glomerular enzyme is membrane-bound
Manually annotated by BRENDA team
-, Q9I7I4
isoform B is expressed as a soluble protein
-
Manually annotated by BRENDA team
MOLECULAR WEIGHT
MOLECULAR WEIGHT MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
90000
-
-
gel filtration
92000
-
-
gel filtration
94000
-
-
-
97000
-
-
-
113000
-
-, Q9I7I4
isoform B, SDS-PAGE using purified NEP4 antiserum
120000
-
-, Q9I7I4
isoform A, SDS-PAGE using purified NEP4 antiserum
270000
320000
-
gel filtration
280000
-
-
brain enzyme, gel filtration
320000
-
-
kidney enzyme, gel filtration
SUBUNITS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
?
-
x * 91000, SDS-PAGE
?
-
x * 87000, brain enzyme, SDS-PAGE
?
-
x * 89000, kidney enzyme, SDS-PAGE
?
-
x * 104000, enzyme from glomeruli, SDS-PAGE; x * 94000, enzyme from tubules, SDS-PAGE
tetramer
-
probably 4 * 81000, SDS-PAGE in presence of 2-mercaptoethanol
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
side-chain modification
-
glycoprotein
side-chain modification
-
six potential N-linked glycosylation sites
side-chain modification
-
the 88000 Da precursor contains four or five N-linked oligosaccharides. The 94000 Da mature enzyme contains sialylated oligosaccharide
side-chain modification
-
glycoprotein
side-chain modification
-
five potential N-linked glycosylation sites
side-chain modification
-
six potential N-linked glycosylation sites
side-chain modification
-
-
side-chain modification
-
glycoprotein
side-chain modification
-
contains 13% carbohydrate
side-chain modification
-
brain enzyme contains 13% carbohydrate, if glucose is excluded
side-chain modification
-
kidney enzyme contains 15% carbohydrate, if glucose is excluded
Crystallization/COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
3D-QSAR studies on mercaptodipeptide inhibitors, using CoMFA and CoMSIA techniques and based on data of PDB entry 1R1I
-
crystal structures of the soluble extracellular domain of neprilysin (residues 52-749) complexed with various potent and competitive inhibitors. Vapour diffusion with 25% PEG 3350, 200 mM ammonium sulfate, 100 mM bis-tris, pH 7.5
-
TEMPERATURE STABILITY
TEMPERATURE STABILITY MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
65
-
-
half-life: 20 min
Purification/COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
Cloned/COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
expressed as a GST-fusion protein in Escherichia coli; expressed as a GST-fusion protein in Escherichia coli
-, Q9I7I4
3 human cDNA types result from alternative splicing of exons 1, 2a, or 2b to the common exon 3
-
expression in 3xTg-AD mice containing, in addition to a PS1M146V knock-in gene, a human APP695 gene carrying the Swedish double mutation and a human four-repeat tau harboring the P30lL mutation
-
expression in amyloid precursor protein transgenic mice
-
expression in mouse brain
-
generation of both neprilysin and amyloid precursor protein transgenic mice
-
overexpression in transgenic mice
-
recombinantly expressed
-
transgenic Drosophila melanogaster expressing human neprilysin and amyloid beta42
-
cloned into the pQE expression vector, resulting in the fusion of a hexahistidine at the N-terminus, expression in Escherichia coli
-
recombinantly expressed
-
EXPRESSION
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
NEP expression is down-regulated in bovine vascular endothelial cells by physiological laminar shear, possibly via a mechanotransduction mechanism involving NADPH oxidase-induced reactive oxygen species production
-
treatment of neuroblastoma cells NB7 with 10 mM L685,458 a potent gamma-secretase inhibitor substantially reduces NEP expression
-
treatment of cells with and histone deacetylase inhibitor sodium valproate or trichostatin A significantly increases NEP mRNA levels and NEP enzymatic activity in neuroblastoma SH-SY5Y cells
-
in neuroblastoma SH-SY5Y cells neprilysin expression is up-regulated estrogen. Upregulation of neprilysin by estrogen is dependent on both estrogen receptor alpha and beta, and ligand-activated estrogen receptor regulates expression of neprilysin through physical interactions between estrogen receptor and estrogen response elements identified in the neprilysin gene
-
decreased expresssion upon treatment with Cu2+
-
ethanol induces an increase in NEP mRNA in the frontal cortex
-
ENGINEERING
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
E535Q
-
inactive enzyme
N542G
-
about 12fold increased Km-value for Leu5,Arg6-enkephalin
R102M
-
about 2fold increased Km-value for Leu5,Arg6-enkephalin, no inhibition by Phe-Gly
R102M/N542G
-
about 20fold increased Km-value for Leu5,Arg6-enkephalin
E584D
-
no activity
E584V
-
no activity
H583F
-
enzymatic activity and Zn-directed inhibitor binding is abolished
H583F
-
loss of activity
H587F
-
enzymatic activity and Zn-directed inhibitor binding is abolished
H587F
-
loss of activity
H637F
-
no effect on activity
V580L
-
change in substrate specificity
E585V
-
inactive
additional information
-
overexpression of human neprilysin for 4 months in young amyloid precursor protein//DeltaPS1 double-transgenic mice results in reduction in amyloid beta peptide levels, attenuation of amyloid load, oxidative stress, and inflammation, and improved spatial orientation. The overall reduction in amyloidosis and associated pathogenetic changes in the brain results in decreased memory impairment by about 50%
additional information
-
sustained expression of a lentiviral vector carrying the neprilysin gene in amyloid precursor protein transgenic mice for up to 6 months lowers not only the amyloid plaque load but also reduces the levels of intracellular amyloid beta immunoreactivity. This is associated with improved behavioral performance in the water maze test and ameliorates the dendritic and synaptic pathology in the amyloid precursor protein transgenic mice
additional information
-
in transgenic Drosophila melanogaster expressing human neprilysin and amyloid beta42, neprilysin efficiently suppresses the formation of intraneuronal amyloid beta42 deposits and amyloid beta42-induced neuron loss. Neuronal neprilysin overexpression reduces cAMP-responsive element-binding protein-mediated transcription, causes age-dependent axon degeneration, and shortens the life span of the flies. The mRNA levels of endogenous fly neprilysin genes and phosphoramidon-sensitive neprilysin activity decline during aging in fly brains
additional information
-
expression of neprilysin on the surface of leukocytes in mouse model of Alzheimer's disease reduces soluble brain amyloid beta peptide levels by 30% and lowers the accumulation of amyloid beta peptides by 50-60% when transplantation is performed at both young and early adult age. Peripheral neprilysin expression reduces amyloid-dependent performance deficits as measured by the Morris water maze test. Neprilysin expression results in the catabolism of amyloid beta to small, innocuous peptide fragments
additional information
-
overexpression neprilysin at low levels in transgenic mouse affects primarily the levels of neuropeptide Y compared with other neuropeptides. Neprilysin cleaves neuropeptide Y in C-terminal fragments, whereas silcencing neprilysin reduces neuropeptide Y processing. Infusion of the most abundant neuropeptide Y fragments 21-36 and 31-36 into the brain of amyloid precursor protein transgenic mice ameliorates the neurodegenerative pathology in this model. The amidated neuropeptide Y fragments protect human neuronal cultures from the neurotoxic effects of amyloid beta
additional information
-
in both neprilysin and amyloid precursor protein transgenic mice, neprilysin overexpression reduces soluble amyloid beta levels by 50% and effectively prevents early amyloid beta deposition in the neocortex and hippocampus. However, it does not reduce levels of amyloid beta trimers and amyloid beta*56 or improve deficits in spatial learning and memory. Neprilysin-dependent degradation of amyloid beta may affect plaques more than oligomers and these structures may form through distinct assembly mechanisms
H587Q
-
inactive enzyme
additional information
-
in neprilysin null mice, loss of neprilysin has no effect on baseline airway or alveolar wall architecture, vessel density, cardiac function, hematocrit, or other relevant peptidases. Only lung neuroendocrine cell hyperplasia and a subtle neuropeptide imbalance are found. After chronic hypoxia, neprilysin-null mice exhibit exaggerate pulmonary hypertension and striking increases in muscularization of distal vessels. Subtle thickening of proximal media/adventitia is also detected. Adaptive right ventricular hypertrophy is less than anticipated. Hypoxic wild-type pulmonary vessels display close temporal and spatial relationships between decreased neprilysin and increased cell growth. Smooth muscle cells from neprilysin-null pulmonary arteries have increased proliferation compared with controls, which is decreased by neprilysin replacement
additional information
-
after chronic constriction injury of the right sciatic nerve, neprilysin knock-out mice are more sensitive to heat, to mechanical stimuli, and to cold than wild type mice. Tissue injury without nerve injury produced no differences between genotypes. After chronic constriction injury, neprilysin knock-out mice show increased hind paw edema but lower skin temperatures than wild type mice. Substance P and endothelin 1 are increased in sciatic nerves. Tissue calcitonin gene related peptide content does not differ between the genotypes
additional information
-
double-mutated mice carrying a targeted depletion of one allele of Mme, the gene encoding neprilysin, and over-expressing human amyloid precursor protein APP, exhibit a reinforced amyloid pathology in comparison with their APP transgenic littermates. In contrast to their parental lines, these mice are impaired in the Morris water maze learning and memory paradigm and show facilitated extinction in the conditioned taste aversion test
APPLICATION
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
medicine
-
overexpression of human neprilysin for 4 months in young amyloid precursor protein//DeltaPS1 double-transgenic mice results in reduction in amyloid beta peptide levels, attenuation of amyloid load, oxidative stress, and inflammation, and improved spatial orientation. The overall reduction in amyloidosis and associated pathogenetic changes in the brain results in decreased memory impairment by about 50%
medicine
-
sustained expression of a lentiviral vector carrying the neprilysin gene in amyloid precursor protein transgenic mice for up to 6 months lowers not only the amyloid plaque load but also reduces the levels of intracellular amyloid beta immunoreactivity. This is associated with improved behavioral performance in the water maze test and ameliorates the dendritic and synaptic pathology in the amyloid precursor protein transgenic mice
medicine
-
CD10, i.e. beta-secretase, expression is detected in 62.2% of prostate cancer samples and occurs preferentially in higher Gleason pattern. CD10 expression positively correlates with adverse tumor features such as elevated preoperative prostate-specific antigen, higher Gleason score, and advanced stage. Prostate-specific antigen recurrence is significantly associated with the staining pattern of CD10 expression. Outcome significantly declines from negative over membranous, membranous-cytoplasmic, to exclusively cytoplasmatic CD10 expression. In multivariate analysis, CD10 expression is an independent predictor for prostate-specific antigen failure
medicine
-
expression of neprilysin on the surface of leukocytes in mouse model of Alzheimer's disease reduces soluble brain amyloid beta peptide levels by 30% and lowers the accumulation of amyloid beta peptides by 50-60% when transplantation is performed at both young and early adult age. Peripheral neprilysin expression reduces amyloid-dependent performance deficits as measured by the Morris water maze test. Neprilysin expression results in the catabolism of amyloid beta to small, innocuous peptide fragments
medicine
-
overexpression neprilysin at low levels in transgenic mouse affects primarily the levels of neuropeptide Y compared with other neuropeptides. Neprilysin cleaves neuropeptide Y in C-terminal fragments, whereas silcencing neprilysin reduces neuropeptide Y processing. Infusion of the most abundant neuropeptide Y fragments 21-36 and 31-36 into the brain of amyloid precursor protein transgenic mice ameliorates the neurodegenerative pathology in this model. The amidated neuropeptide Y fragments protect human neuronal cultures from the neurotoxic effects of amyloid beta
medicine
-
in the Flemish variant of amyloid beta, resistance to degradation by nepriylsin may underlie the pathogenicity associated with the A21G mutantion in amyloid beta
molecular biology
-
the established assay is extremely sensitive to neprilysin, but insensitive, or much less sensitive, to other Abeta-degrading enzymes. As low as 0.1 nM of neprilysin can be detected
medicine
-
neprilysin can reduce the size and number of Abeta deposits in a transgenic mouse model. Neprilysin gene transfer therapy or other methods to increase endogenous neprilysin activity have the potential to prevent the accumulation of the amyloid Abeta peptide and as such may be able to prevent or delay the onset of Alzheimer#s disease
medicine
-
impaired cardiopulmonary vagal reflex control of heart rate is a feature of normal aging, and this deficit may be ameliorated by either atrium natriuretic peptide infusion or chronic neutral endopeptidase inhibition
pharmacology
-
inhibitor thiorphan might be effective for reducing elevated A-type natriuretic peptide levels in sepsis. Plasma and lung A-type natriuretic peptide levels in rats treated with lipopolysaccharide are significantly higher than those in the control group, but are significantly decreased by thiorphan administration. Natriuretic peptide receptor-A mRNA levels do not differ significantly among the groups. Natriuretic peptide receptor-C mRNA levels in animals treated with lipopolysaccharide plus thiorphan group are significantly higher than those in the other groups