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(7-methoxycoumarin-4-yl)acetyl-Arg-Pro-Pro-Gly-Phe-Ser-Ala-Phe-Lys(2,4-dinitrophenyl) + H2O
?
a bradykinin-based peptide substrate QFS
-
-
?
(7-methoxycoumarin-4-yl)acetyl-Arg-Pro-Pro-Gly-Phe-Ser-Ala-Phe-Lys-(2,4-dinitrophenyl) + H2O
(7-methoxycoumarin-4-yl)acetyl-Arg-Pro-Pro-Gly-Phe-Ser-Ala + Phe-Lys-(2,4-dinitrophenyl)
bradykinin-based quenched fluorescent substrate assay
-
-
?
2 KFRRQRPRLSHKGPMPF + 2 H2O
KFRRQRPR + LSHKGPMPF + KFRRQRPRL + SHKGPMPF
-
-
-
ir
2 LVQPRGSRNGPGPWQGGRRKFRRQRPRLSHKGPMPF + 2 H2O
LVQPRGSRNGPGPWQGGRRKFRRQRPRL + SHKGPMPF + LVQPRGSRNGPGPWQGGRRKFRRQRPR + LSHKGPMPF
-
-
-
ir
2 pGlu-RPRLSHKGPMPF + 2 H2O
pGlu-RPRL + pGlu-RPR + SHKGPMPF + LSHKGPMPF
-
-
-
ir
2-aminobenzoyl-ARFK-2,4-dinitrophenyl ester + H2O
2-aminobenzoyl-AR + FK-2,4-dinitrophenyl ester
-
-
-
-
ir
2-aminobenzoyl-DRFK-2,4-dinitrophenyl ester + H2O
2-aminobenzoyl-DR + FK-2,4-dinitrophenyl ester
-
-
-
-
ir
2-aminobenzoyl-FRFK-2,4-dinitrophenyl ester + H2O
2-aminobenzoyl-FR + FK-2,4-dinitrophenyl ester
-
-
-
-
ir
2-aminobenzoyl-HRFK-2,4-dinitrophenyl ester + H2O
2-aminobenzoyl-HR + FK-2,4-dinitrophenyl ester
-
-
-
-
ir
2-aminobenzoyl-IRFK-2,4-dinitrophenyl ester + H2O
2-aminobenzoyl-IR + FK-2,4-dinitrophenyl ester
-
-
-
-
ir
2-aminobenzoyl-KRFK-2,4-dinitrophenyl ester + H2O
2-aminobenzoyl-KR + FK-2,4-dinitrophenyl ester
-
-
-
-
ir
2-aminobenzoyl-LRFK-2,4-dinitrophenyl ester + H2O
2-aminobenzoyl-LR + FK-2,4-dinitrophenyl ester
-
-
-
-
ir
2-aminobenzoyl-NRFK-2,4-dinitrophenyl ester + H2O
2-aminobenzoyl-NR + FK-2,4-dinitrophenyl ester
-
-
-
-
ir
2-aminobenzoyl-RAFK-2,4-dinitrophenyl ester + H2O
2-aminobenzoyl-RA + FK-2,4-dinitrophenyl ester
-
-
-
-
ir
2-aminobenzoyl-RDFK-2,4-dinitrophenyl ester + H2O
2-aminobenzoyl-RD + FK-2,4-dinitrophenyl ester
-
-
-
-
ir
2-aminobenzoyl-REFK-2,4-dinitrophenyl ester + H2O
2-aminobenzoyl-RE + FK-2,4-dinitrophenyl ester
-
-
-
-
ir
2-aminobenzoyl-rGF-N-(2,4-dinitrophenyl)ethylenediamine + H2O
2-aminobenzoyl-D-Arg-Gly + Phe-N-(2,4-dinitrophenyl)ethylenediamine
-
-
-
-
ir
2-aminobenzoyl-RGFK(Dnp)-OH + H2O
2-aminobenzoyl-RG + FK-2,4-dinitrophenyl ester
-
-
-
-
ir
2-aminobenzoyl-RGFK-2,4-dinitrophenyl amide + H2O
2-aminobenzoyl-RG + FK-2,4-dinitrophenyl amide
-
-
-
-
ir
2-aminobenzoyl-RGFK-2,4-dinitrophenyl ester + H2O
2-aminobenzoyl-RG + FK-2,4-dinitrophenyl ester
-
-
-
-
ir
2-aminobenzoyl-rGL-N-(2,4-dinitrophenyl)ethylenediamine + H2O
2-aminobenzoyl-D-Arg-Gly + Leu-N-(2,4dinitrophenyl)ethylenediamine
-
-
-
-
ir
2-aminobenzoyl-rGV-N-(2,4-dinitrophenyl)ethylenediamine + H2O
2-aminobenzoyl-D-Arg-Gly + Val-N-(2,4-dinitrophenyl)ethylenediamine
-
-
-
-
ir
2-aminobenzoyl-RHFK-2,4-dinitrophenyl ester + H2O
2-aminobenzoyl-RH + FK-2,4-dinitrophenyl ester
-
-
-
-
ir
2-aminobenzoyl-RKFK-2,4-dinitrophenyl ester + H2O
2-aminobenzoyl-RK + FK-2,4-dinitrophenyl ester
-
-
-
-
ir
2-aminobenzoyl-RNFK-2,4-dinitrophenyl ester + H2O
2-aminobenzoyl-RN + FK-2,4-dinitrophenyl ester
-
-
-
-
ir
2-aminobenzoyl-RPFK-2,4-dinitrophenyl ester + H2O
2-aminobenzoyl-RP + FK-2,4-dinitrophenyl ester
-
-
-
-
ir
2-aminobenzoyl-RQFK-2,4-dinitrophenyl ester + H2O
2-aminobenzoyl-RQ + FK-2,4-dinitrophenyl ester
-
-
-
-
ir
2-aminobenzoyl-RRFK-2,4-dinitrophenyl amide + H2O
2-aminobenzoyl-RR + FK-2,4-dinitrophenyl amide
-
-
-
-
ir
2-aminobenzoyl-RRFK-2,4-dinitrophenyl ester + H2O
2-aminobenzoyl-RR + FK-2,4-dinitrophenyl ester
-
-
-
-
ir
2-aminobenzoyl-rRL-N-(2,4-dinitrophenyl)ethylenediamine + H2O
2-aminobenzoyl-D-Arg-L-Arg + Leu-N-(2,4-dinitrophenyl)ethylenediamine
-
-
-
-
ir
2-aminobenzoyl-RSFK-2,4-dinitrophenyl ester + H2O
2-aminobenzoyl-RS + FK-2,4-dinitrophenyl ester
-
-
-
-
ir
2-aminobenzoyl-rSL-N-(2,4-dinitrophenyl)ethylenediamine + H2O
2-aminobenzoyl-D-Arg-L-Ser + Leu-N-(2,4-dinitrophenyl)ethylenediamine
-
-
-
-
ir
2-aminobenzoyl-RTFK-2,4-dinitrophenyl ester + H2O
2-aminobenzoyl-RT + FK-2,4-dinitrophenyl ester
-
-
-
-
ir
2-aminobenzoyl-SRFK-2,4-dinitrophenyl ester + H2O
2-aminobenzoyl-SR + FK-2,4-dinitrophenyl ester
-
-
-
-
ir
2-aminobenzoyl-TRFK-2,4-dinitrophenyl ester + H2O
2-aminobenzoyl-TR + FK-2,4-dinitrophenyl ester
-
-
-
-
ir
2-aminobenzoyl-VRFK-2,4-dinitrophenyl ester + H2O
2-aminobenzoyl-VR + FK-2,4-dinitrophenyl ester
-
-
-
-
ir
2-aminobenzoyl-WRFK-2,4-dinitrophenyl ester + H2O
2-aminobenzoyl-WR + FK-2,4-dinitrophenyl ester
-
-
-
-
ir
2-aminobenzoyl-YRFK-2,4-dinitrophenyl ester + H2O
2-aminobenzoyl-YR + FK-2,4-dinitrophenyl ester
-
-
-
-
ir
Abz-QRPRLSH-(3-nitro)Tyr + H2O
Abz-QRPRL + Ser-His-(3-nitro)Tyr
-
-
-
ir
adrenocorticotropic hormone + H2O
?
-
-
-
-
?
adrenomedullin + H2O
?
-
-
-
?
Ala-Leu-enkephalin + H2O
?
-
-
-
-
?
Aldolase + H2O
?
-
-
-
-
?
alpha-endorphin + H2O
?
-
-
-
?
alpha-neoendorphin + H2O
?
amyloid beta peptide + H2O
?
amyloid beta peptide Abeta42 + H2O
?
-
the peptide primarily undergoes degradation by NEP in vivo in the brain
-
-
?
amyloid beta peptide1-40 + H2O
?
amyloid beta peptide1-40 + H2O
amyloid beta peptide Asp1-Lys16 + amyloid beta peptide Asp1-Leu17 + amyloid beta peptide Asp1-Phe19
the wild-type enzyme cleaves Ab1-40 predominantly at Lys16-Leu17, Leu17-Val18 and Phe19-Phe20. The mutant G399V/G714K cleaves preferentially at Phe20-Ala21
main cleavage fragments after 60 min with the wild-type enzyme. After 360 min these fragments are degraded further, accompanied by the appearance of Val12-Leu17 and Tyr10-Leu17 fragments
-
?
amyloid beta peptide1-42 + H2O
?
amyloid beta(1-40) mutant A21G + H2O
?
-
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
?
-
Iowa variant of amyloid beta
-
-
?
amyloid beta(1-40) mutant E22G + H2O
?
-
Arctic variant of amyloid beta
-
-
?
amyloid beta(1-40) mutant E22K + H2O
?
-
Italian variant of amyloid beta
-
-
?
amyloid beta(1-40) mutant E22Q + H2O
?
-
Dutch variant of amyloid beta
-
-
?
amyloid beta(1-40) peptide + H2O
?
-
-
-
-
?
amyloid-beta(1-7)AAC + H2O
?
a synthetic peptide, design and synthesis of a quenched fluorogenic peptide substrate qf-Abeta(1-7)AAC (with the sequence VHHQKAAC), which has a fluorophore, Alexa-350, linked to the side-chain of its C-terminal cysteine and a quencher, Dabcyl, linked to its N-terminus
-
-
?
amyloid-beta(12-16)AAC + H2O
?
a synthetic peptide, design and synthesis of a quenched fluorogenic peptide substrate qf-Abeta(12-16)AAC (with the sequence VHHQKAAC), which has a fluorophore, Alexa-350, linked to the side-chain of its C-terminal cysteine and a quencher, Dabcyl, linked to its N-terminus. This peptide emits strong fluorescence upon cleavage. qf-Abeta(12-16)AAC is more sensitive to NEP than the previously reported peptide substrates, so that concentrations of NEP as low as 0.03 nM can be detected at peptide concentration of 0.002 mM
-
-
?
amyloid-beta1-40 + H2O
Abeta1-16 + Abeta 1-17 + Abeta1-19
-
-
-
?
amyloid-beta4-40 + H2O
?
a synthetic peptide
-
-
?
amyloid-beta4-42 + H2O
?
a synthetic peptide
-
-
?
angiotensin + H2O
?
-
-
-
?
angiotensin III + H2O
?
-
-
-
-
?
angiotensin(1-9) + H2O
?
-
-
-
-
?
Arg-Pro-Lys-Pro-Gln-Gln-Phe-Phe-Gly-Leu-Met-NH2 + H2O
?
Arg-vasopressin + H2O
?
-
-
-
?
Asp-Tyr(SO3H)-Met-Gly-Trp-Met-Asp-PheNH2 + H2O
?
Atrial natriuretic factor + H2O
?
atrial natriuretic peptide + H2O
?
azocasein + H2O
?
-
-
-
-
?
Azocoll + H2O
?
-
-
-
-
?
benzoyl-Gly-Gly-Arg-Leu-2-naphthylamide + H2O
benzoyl-Gly-Gly-Arg + L-Leu-2-naphthylamide
-
-
-
-
?
benzyloxycarbonyl-Ala-Gly-Leu-Ala + H2O
?
-
-
-
-
?
benzyloxycarbonyl-Phe-Arg-4-methyl-7-coumarylamide + H2O
?
-
-
-
-
?
beta-amyloid peptide + H2O
?
-
-
-
-
?
beta-endorphin + H2O
?
-
-
-
-
?
beta-lipotropin(61-69) + H2O + H2O
?
beta-neoendorphin + H2O
?
brain natriuretic peptide + H2O
?
-
-
-
?
cholecystokinin-8 + H2O
?
D-Ala2-Leu5-enkephalin + H2O
?
-
-
-
-
?
D-Ala2-Leu5-enkephalin + H2O
Tyr-D-Ala-Gly + Phe-Leu
D-Ala2-Leu5-enkephalinamide + H2O
?
-
-
-
-
?
dansyl-Gly-Trp-Gly + H2O
dansyl-Gly + Trp-Gly
-
-
-
?
dansyl-Gly-Tyr-Gly + H2O
dansyl-Gly + Tyr-Gly
-
-
-
?
dansyl-Gly-Tyr-Gly-NH2 + H2O
dansyl-Gly + Tyr-Gly-NH2
-
-
-
-
?
dynorphin A-10 + H2O
?
-
-
-
-
?
dynorphin A-13 + H2O
?
-
-
-
-
?
dynorphin A-17 + H2O
?
-
-
-
-
?
dynorphin A-6 + H2O
?
-
-
-
-
?
dynorphin A-8 + H2O
?
-
-
-
-
?
dynorphin A-9 + H2O
?
-
-
-
-
?
dynorphin(1-9) + H2O
?
-
-
-
-
?
exendin-4 + H2O
?
-
poor substrate
-
-
?
fibrinogen + H2O
fibrin + ?
galanin + H2O
?
-
-
-
-
?
gastri-releasing peptide + H2O
?
-
-
-
?
gastric inhibitor peptide + H2O
?
-
poor substrate
-
-
?
gastrin releasing peptide-10 + H2O
?
GLP-1(7-36)amide + H2O
?
-
insulinotropic peptide hormone
-
-
?
glucagon-like peptide 1 + H2O
?
-
-
-
-
?
glutaryl-Ala-Ala-Phe-2-naphthylamide + H2O
glutaryl-Ala-Ala + Phe-2-naphthylamide
-
-
-
?
glutaryl-Ala-Ala-Phe-4-methoxy-2-naphthylamide + H2O
glutaryl-Ala-Ala + Phe-4-methoxy-2-naphthylamide
glutaryl-Ala-Ala-Phe-4-methoxy-2-naphthylamine + H2O
?
-
-
-
-
?
glutaryl-Gly-Gly-Phe-2-naphthylamide + H2O
glutaryl-Gly-Gly + Phe-2-naphthylamide
-
-
-
?
glutaryl-Gly-Gly-Phe-2-naphthylamide + H2O
glutaryl-Gly-Gly-Phe + 2-naphthylamine
-
-
-
-
?
Gly-Trp-Gly + H2O
?
-
-
-
-
?
haemoglobin + H2O
?
-
-
-
-
?
hippuryl-Arg-Arg-Ala-2-naphthylamide + H2O
hippuryl-Arg-Arg + Ala-2-naphthylamide
-
-
-
-
?
hippuryl-Arg-Arg-Leu-2-naphthylamide + H2O
hippuryl-Arg-Arg + Leu-2-naphthylamide
His-Lys-Thr-Asp-Ser-Phe-Val-Gly-Leu-Met-NH2 + H2O
His-Lys-Thr-Asp-Ser + Phe-Val-Gly + Leu-Met-NH2
interleukin 1beta + H2O
?
Leu-2-naphthylamide + H2O
?
-
-
-
-
?
Leu-enkephalin + H2O
?
-
-
-
-
?
Leu5-enkephalin-Arg6 + H2O
?
-
-
-
-
?
Leu5-enkephalinamide + H2O
?
leucine5-enkephalin + H2O
?
Tyr-Gly-Gly-Phe-Leu is cleaved at the Gly-Phe bond by the wild-type enzyme
-
-
?
Luliberin + H2O
?
-
poor substrate
-
-
?
Luteinizing hormone-releasing hormone + H2O
?
Mca-Arg-Pro-Pro-Gly-Phe-Ser-Ala-Phe-Lys-(Dnp)-OH + H2O
?
Mca-RPPGFSAFK-(Dnp) + H2O
?
-
-
-
?
Met-enkephalin + H2O
?
-
-
-
-
?
Met-enkephalin amide + H2O
?
-
-
-
-
?
Met-enkephalin-Arg6-Gly7-Leu + H2O
?
Met5-enkephalin-Arg6 + H2O
?
-
-
-
-
?
Met5-enkephalin-Arg6-Phe7 + H2O
?
N-(4-carboxy-1-oxobutyl)-L-alanyl-L-alanyl-N-(4-methoxy-2-naphthalenyl)-L-phenylalaninamide + H2O
N-(4-carboxy-1-oxobutyl)-L-alanyl-L-alanyl-L-phenylalanine + 4-methoxy-2-naphthylamine
-
-
-
?
N-acetyl-Gly-Trp-Gly + H2O
N-acetyl-Gly + Trp-Gly
-
-
-
-
?
N-benzyloxycarbonyl-Gly-Gly-Leu 2-naphthylamide + H2O
N-benzyloxycarbonyl-Gly-Gly + L-leucine 2-naphthylamide
-
-
-
?
N-benzyoxycarbonyl-Gly-Gly-Leu 2-naphthylamide + H2O
?
-
-
-
-
?
N-benzyoxycarbonyl-Gly-Gly-Leu-2-naphthylamide + H2O
N-benzyoxycarbonyl-Gly-Gly + L-Leu-2-naphthylamide
-
-
-
-
?
N-dansyl-Ala-Gly-D-(4-nitro-Phe)-Gly + H2O
?
-
-
-
-
?
N-dansyl-D-Ala-Gly-p-nitrophenyl-Ala-Gly + H2O
?
N-formyl-L-Met-Leu-Phe + H2O
?
-
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
-
-
-
?
Na,K-ATPase alpha subunit + H2O
?
-
-
-
-
?
Nalpha-benzoyl-Gly-Arg-Arg-Ala-2-naphthylamide + H2O
Nalpha-benzoyl-Gly-Arg-Arg + Ala-2-naphthylamide
-
-
-
?
Nalpha-benzoyl-Gly-Arg-Arg-Leu-2-naphthylamide + H2O
Nalpha-benzoyl-Gly-Arg-Arg + Leu-2-naphthylamide
-
-
-
?
Nalpha-benzoyl-Gly-Arg-Arg-Phe-2-naphthylamide + H2O
Nalpha-benzoyl-Gly-Arg-Arg + Phe-2-naphthylamide
-
-
-
?
Nalpha-benzoyl-Gly-Arg-Leu-2-naphthylamide + H2O
Nalpha-benzoyl-Gly-Arg + Leu-2-naphthylamide
-
-
-
?
Nalpha-benzoyl-Gly-Gly-Arg-Leu-2-naphthylamide + H2O
Nalpha-benzoyl-Gly-Gly-Arg + Leu-2-naphthylamide
-
-
-
?
Nalpha-benzoyl-Gly-Lys-Arg-Arg-Leu-2-naphthylamide + H2O
Nalpha-benzoyl-Gly-Lys-Arg-Arg + Leu-2-naphthylamide
-
-
-
?
Nalpha-benzoyl-Gly-Lys-Lys-Arg-Arg-Leu-2-naphthylamide + H2O
Nalpha-benzoyl-Gly-Lys-Lys-Arg-Arg + Leu-2-naphthylamide
-
-
-
?
Neurokinin A + H2O
?
-
-
-
?
neuropeptide Y + H2O
truncated neuropeptide Y + C-terminal fragments of neuropeptide Y
-
-
neuropeptide Y 21-36 and 31-36 are the most abundant fragments generated in vivo
-
?
nociceptin + H2O
?
-
-
-
?
pBNP-26 + H2O
?
-
cleaved at several sites
-
-
?
pulmonary vasodilative vasoactive intestinal peptide + H2O
?
rapid inactivation
-
-
?
pyroglutamyl-Leu-Asn-Phe-Thr-Pro-Asn-Trp-Gly-Thr-NH2 + H2O
pyroglutamyl-Leu-Asn + Phe-Thr-Pro-ASn-Trp-Gly-Thr-NH2
Secretin + H2O
?
-
-
-
-
?
somatostatin 14 + H2O
?
-
-
-
?
somatostatin 28 + H2O
?
-
-
-
?
striatal natriuretic factor + H2O
?
-
-
-
-
?
succinyl-Ala-Ala-Phe-4-methylcoumarin 7-amide + H2O
succinyl-Ala-Ala + Phe-4-methylcoumarin 7-amide
succinyl-Ala-Ala-Phe-7-amido-4-methylcoumarin + H2O
?
succinyl-Ala-Ala-Phe-7-amido-4-methylcoumarin + H2O
succinyl-Ala-Ala-Phe + 7-amino-4-methylcoumarin
succinyl-Ala-Ala-Phe-p-nitroanilide + H2O
?
-
-
-
-
?
succinyl-Arg-Arg-Leu-2-naphthylamide + H2O
succinyl-Arg-Arg + Leu-2-naphthylamide
-
-
-
?
succinyl-Arg-Pro-Phe-His-Leu-Leu-Val-Tyr-7-amido-4-methylcoumarin + H2O
?
-
-
-
-
?
sulfated cholecystokinin octapeptide + H2O
?
-
-
-
-
?
tachykinin + H2O
?
Q9I7I4
27.8% degradation
-
-
?
Tyr-D-Ala-Gly-Phe-Leu + H2O
Tyr-D-Ala-Gly + Phe-Leu
-
-
-
?
Tyr-D-Ala-Gly-Phe-Met + H2O
Tyr-D-Ala-Gly + Phe-Met
Tyr-D-Ala-Gly-Phe-Met-NH2 + H2O
Tyr-D-Ala-Gly + Phe-Met-NH2
Tyr-Gly-Gly-Phe-Met + H2O
Tyr-Gly-Gly + Phe-Met
Vasoactive intestinal peptide + H2O
?
-
-
-
-
?
Z-Ala-Ala-Leu-4-nitroanilide + H2O
Z-Ala-Ala-Leu + 4-nitroaniline
-
-
-
?
additional information
?
-
alpha-neoendorphin + H2O
?
-
-
-
-
?
alpha-neoendorphin + H2O
?
-
-
-
-
?
alpha-neoendorphin + H2O
?
-
-
-
-
?
alpha-neoendorphin + H2O
?
-
-
-
-
?
amyloid beta peptide + H2O
?
-
-
-
?
amyloid beta peptide + H2O
?
-
-
-
-
?
amyloid beta peptide + H2O
?
cleavage sites, overview
-
-
?
amyloid beta peptide + H2O
?
degradation
-
-
?
amyloid beta peptide1-40 + H2O
?
degradation
-
-
?
amyloid beta peptide1-40 + H2O
?
multiple cleavage sites
-
-
?
amyloid beta peptide1-40 + H2O
?
multiple cleavage sites, product peaks corresponding to Abeta1-16, Abeta1-17, Abeta10-17, Abeta20-28, Abeta20-29, and Abeta20-30. The C-terminal products result from the cleavages at K28-G29, G29-A30, and A30-I31. These products are derived from the trans-membrane region of the amyloid precursor protein (APP) from which Abeta is formed and are rather hydrophobic
-
-
?
amyloid beta peptide1-42 + H2O
?
-
-
-
?
amyloid beta peptide1-42 + H2O
?
-
-
-
-
?
amyloid beta peptide1-42 + H2O
?
degradation
-
-
?
amyloid beta peptide1-42 + H2O
?
multiple cleavage sites
-
-
?
amyloid-beta + H2O
?
-
-
-
?
amyloid-beta + H2O
?
degradation
-
-
ir
amyloid-beta1-40 + H2O
?
a synthetic peptide
-
-
?
amyloid-beta1-40 + H2O
?
degradation
-
-
ir
amyloid-beta1-42 + H2O
?
a synthetic peptide
-
-
?
amyloid-beta1-42 + H2O
?
degradation
-
-
ir
angiotensin I + H2O
?
Q9I7I4
51.6% degradation
-
-
?
angiotensin I + H2O
?
-
-
-
-
?
angiotensin I + H2O
?
-
-
-
-
?
angiotensin I + H2O
?
-
-
-
-
?
angiotensin I + H2O
?
-
-
-
-
?
angiotensin II + H2O
?
-
-
-
-
?
angiotensin II + H2O
?
-
-
-
-
?
angiotensin II + H2O
?
-
-
-
-
?
Arg-Pro-Lys-Pro-Gln-Gln-Phe-Phe-Gly-Leu-Met-NH2 + H2O
?
-
-
-
-
?
Arg-Pro-Lys-Pro-Gln-Gln-Phe-Phe-Gly-Leu-Met-NH2 + H2O
?
-
-
-
-
?
Arg-Pro-Lys-Pro-Gln-Gln-Phe-Phe-Gly-Leu-Met-NH2 + H2O
?
-
-
-
-
?
Arg-Pro-Lys-Pro-Gln-Gln-Phe-Phe-Gly-Leu-Met-NH2 + H2O
?
-
-
-
-
?
Arg-Pro-Lys-Pro-Gln-Gln-Phe-Phe-Gly-Leu-Met-NH2 + H2O
?
-
-
-
-
?
Arg-Pro-Lys-Pro-Gln-Gln-Phe-Phe-Gly-Leu-Met-NH2 + H2O
?
-
i.e. substance P, seven peptides are produced
-
-
?
Asp-Tyr(SO3H)-Met-Gly-Trp-Met-Asp-PheNH2 + H2O
?
-
-
-
-
?
Asp-Tyr(SO3H)-Met-Gly-Trp-Met-Asp-PheNH2 + H2O
?
-
-
-
-
?
Asp-Tyr(SO3H)-Met-Gly-Trp-Met-Asp-PheNH2 + H2O
?
-
-
-
-
?
Asp-Tyr(SO3H)-Met-Gly-Trp-Met-Asp-PheNH2 + H2O
?
-
-
-
-
?
Asp-Tyr(SO3H)-Met-Gly-Trp-Met-Asp-PheNH2 + H2O
?
-
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
?
-
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
?
-
-
-
-
?
Atrial natriuretic factor + H2O
?
-
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
?
-
-
-
-
?
Atrial natriuretic factor + H2O
?
-
-
-
-
?
Atrial natriuretic factor + H2O
?
-
dominant enzyme in the hydrolysis of atrial natriuretic factor
-
-
?
atrial natriuretic peptide + H2O
?
-
-
-
?
atrial natriuretic peptide + H2O
?
-
no activity with brain natriuretic peptide
-
-
?
atrial natriuretic peptide + H2O
?
-
-
-
-
?
beta-lipotropin(61-69) + H2O + H2O
?
-
-
-
-
?
beta-lipotropin(61-69) + H2O + H2O
?
-
-
-
-
?
beta-lipotropin(61-69) + H2O + H2O
?
-
-
-
-
?
beta-neoendorphin + H2O
?
-
-
-
-
?
beta-neoendorphin + H2O
?
-
-
-
-
?
beta-neoendorphin + H2O
?
-
-
-
-
?
beta-neoendorphin + H2O
?
-
-
-
-
?
bradykinin + H2O
?
Q9I7I4
27.8% degradation
-
-
?
bradykinin + H2O
?
-
-
-
-
?
bradykinin + H2O
?
-
-
-
?
bradykinin + H2O
?
-
-
-
-
?
bradykinin + H2O
?
-
-
-
?
bradykinin + H2O
?
-
-
-
-
?
bradykinin + H2O
?
-
-
-
-
?
bradykinin + H2O
?
-
-
-
-
?
bradykinin + H2O
?
-
-
-
-
?
cholecystokinin-8 + H2O
?
-
-
-
-
?
cholecystokinin-8 + H2O
?
-
-
-
-
?
D-Ala2-Leu5-enkephalin + H2O
Tyr-D-Ala-Gly + Phe-Leu
-
i.e. Tyr-D-Ala-Gly-Phe-Leu
-
?
D-Ala2-Leu5-enkephalin + H2O
Tyr-D-Ala-Gly + Phe-Leu
-
i.e. Tyr-D-Ala-Gly-Phe-Leu
-
-
?
D-Ala2-Leu5-enkephalin + H2O
Tyr-D-Ala-Gly + Phe-Leu
-
i.e. Tyr-D-Ala-Gly-Phe-Leu
-
-
?
D-Ala2-Leu5-enkephalin + H2O
Tyr-D-Ala-Gly + Phe-Leu
-
i.e. Tyr-D-Ala-Gly-Phe-Leu
-
-
?
D-Ala2-Leu5-enkephalin + H2O
Tyr-D-Ala-Gly + Phe-Leu
-
i.e. Tyr-D-Ala-Gly-Phe-Leu
-
-
?
D-Ala2-Leu5-enkephalin + H2O
Tyr-D-Ala-Gly + Phe-Leu
-
i.e. Tyr-D-Ala-Gly-Phe-Leu
-
-
?
dynorphin + H2O
?
-
-
-
-
?
dynorphin + H2O
?
-
dynorphin A-6, A-8, A-9, A-10, A-13 and A-17
-
-
?
dynorphin + H2O
?
-
-
-
-
?
dynorphin + H2O
?
-
-
-
-
?
Elastin + H2O
?
-
-
-
?
endothelin-1 + H2O
?
-
-
-
?
endothelin-1 + H2O
?
-
-
-
-
?
endothelin-1 + H2O
?
-
-
-
?
enkephalin + H2O
?
-
-
-
?
enkephalin + H2O
?
-
hydrolysis at Gly3-Phe4
-
-
?
enkephalin + H2O
?
-
-
-
-
?
enkephalin + H2O
?
-
hydrolysis at Gly3-Phe4
-
-
?
enkephalin + H2O
?
-
hydrolysis at Gly3-Phe4
-
-
?
fibrinogen + H2O
fibrin + ?
inactivation, mechanism of NEP-mediated inactivation of fibrinogen through cleavage of the N-termini of the Aalpha- and Bbeta-chains of fibrinogen thereby significantly impairing initiation of fibrin formation by thrombin, overview
-
-
?
fibrinogen + H2O
fibrin + ?
fibrinogen from human and rat blood plasma, inactivation
-
-
?
FMRF amide + H2O
?
-
-
-
-
?
FMRF amide + H2O
?
-
-
-
-
?
FMRF amide + H2O
?
-
-
-
-
?
gamma-endorphin + H2O
?
-
-
-
-
?
gamma-endorphin + H2O
?
-
-
-
?
gamma-endorphin + H2O
?
-
-
-
-
?
gamma-endorphin + H2O
?
-
-
-
-
?
gastrin + H2O
?
-
-
-
-
?
gastrin + H2O
?
-
-
-
-
?
gastrin + H2O
?
-
-
-
-
?
gastrin G-17 + H2O
?
-
-
-
-
?
gastrin G-17 + H2O
?
-
cleavage at four sites, Trp4-Leu5, Ala11-Tyr12, Gly13-Trp14 and Asp16-Phe17
-
-
?
gastrin G-17 + H2O
?
-
sulfated and unsulfated gastrin, cleavage is faster with the sulfated peptide
-
-
?
gastrin releasing peptide-10 + H2O
?
-
-
-
-
?
gastrin releasing peptide-10 + H2O
?
-
-
-
-
?
gastrin releasing peptide-10 + H2O
?
-
-
-
-
?
Glucagon + H2O
?
-
-
-
-
?
Glucagon + H2O
?
-
-
-
-
?
Glucagon + H2O
?
-
NEP24.11 is an important mediator of the degradation of both endogenous and exogenous glucagon in vivo
-
-
?
glutaryl-Ala-Ala-Phe-4-methoxy-2-naphthylamide + H2O
glutaryl-Ala-Ala + Phe-4-methoxy-2-naphthylamide
-
-
-
?
glutaryl-Ala-Ala-Phe-4-methoxy-2-naphthylamide + H2O
glutaryl-Ala-Ala + Phe-4-methoxy-2-naphthylamide
-
-
-
?
glutaryl-Ala-Ala-Phe-4-methoxy-2-naphthylamide + H2O
glutaryl-Ala-Ala + Phe-4-methoxy-2-naphthylamide
-
-
-
-
?
glutaryl-Ala-Ala-Phe-4-methoxy-2-naphthylamide + H2O
glutaryl-Ala-Ala + Phe-4-methoxy-2-naphthylamide
-
-
-
?
glutaryl-Ala-Ala-Phe-4-methoxy-2-naphthylamide + H2O
glutaryl-Ala-Ala + Phe-4-methoxy-2-naphthylamide
-
-
-
?
hippuryl-Arg-Arg-Leu-2-naphthylamide + H2O
hippuryl-Arg-Arg + Leu-2-naphthylamide
-
-
-
-
?
hippuryl-Arg-Arg-Leu-2-naphthylamide + H2O
hippuryl-Arg-Arg + Leu-2-naphthylamide
-
-
-
-
?
His-Lys-Thr-Asp-Ser-Phe-Val-Gly-Leu-Met-NH2 + H2O
His-Lys-Thr-Asp-Ser + Phe-Val-Gly + Leu-Met-NH2
-
-
-
-
?
His-Lys-Thr-Asp-Ser-Phe-Val-Gly-Leu-Met-NH2 + H2O
His-Lys-Thr-Asp-Ser + Phe-Val-Gly + Leu-Met-NH2
-
-
-
-
?
His-Lys-Thr-Asp-Ser-Phe-Val-Gly-Leu-Met-NH2 + H2O
His-Lys-Thr-Asp-Ser + Phe-Val-Gly + Leu-Met-NH2
-
-
-
-
?
His-Lys-Thr-Asp-Ser-Phe-Val-Gly-Leu-Met-NH2 + H2O
His-Lys-Thr-Asp-Ser + Phe-Val-Gly + Leu-Met-NH2
-
-
-
-
?
His-Lys-Thr-Asp-Ser-Phe-Val-Gly-Leu-Met-NH2 + H2O
His-Lys-Thr-Asp-Ser + Phe-Val-Gly + Leu-Met-NH2
-
i.e. neurokinin A, hydrolysis at two sites: Ser5-Phe6 and Gly8-Leu9
-
-
?
insulin B chain + H2O
?
-
-
-
-
?
insulin B chain + H2O
?
multiple cleavage sites
-
-
?
insulin B chain + H2O
?
multiple cleavage sites, product analysis and cleavage sites preferences of wild-type and mutant neprilysins, cleavage sites, overview
-
-
?
insulin B chain + H2O
?
-
-
-
-
?
insulin B chain + H2O
?
-
-
-
-
?
interleukin 1beta + H2O
?
-
-
-
-
?
interleukin 1beta + H2O
?
-
-
-
-
?
interleukin 1beta + H2O
?
-
-
-
-
?
Leu5-enkephalin + H2O
?
-
-
-
-
?
Leu5-enkephalin + H2O
?
-
-
-
-
?
Leu5-enkephalin + H2O
?
-
-
-
-
?
Leu5-enkephalin + H2O
?
-
-
-
-
?
Leu5-enkephalin + H2O
?
-
-
-
-
?
Leu5-enkephalinamide + H2O
?
-
-
-
-
?
Leu5-enkephalinamide + H2O
?
-
-
-
-
?
Luteinizing hormone-releasing hormone + H2O
?
-
-
-
-
?
Luteinizing hormone-releasing hormone + H2O
?
-
-
-
-
?
Luteinizing hormone-releasing hormone + H2O
?
-
-
-
-
?
Luteinizing hormone-releasing hormone + H2O
?
-
-
-
-
?
Mca-Arg-Pro-Pro-Gly-Phe-Ser-Ala-Phe-Lys-(Dnp)-OH + H2O
?
-
-
-
?
Mca-Arg-Pro-Pro-Gly-Phe-Ser-Ala-Phe-Lys-(Dnp)-OH + H2O
?
-
-
-
?
Met-enkephalin-Arg6-Gly7-Leu + H2O
?
-
-
-
-
?
Met-enkephalin-Arg6-Gly7-Leu + H2O
?
-
-
-
-
?
Met-enkephalin-Arg6-Gly7-Leu + H2O
?
-
-
-
-
?
Met-Leu-Phe + H2O
?
-
chemotactic peptide
-
-
?
Met-Leu-Phe + H2O
?
-
chemotactic peptide
-
-
?
Met-Leu-Phe + H2O
?
-
chemotactic peptide
-
-
?
Met5-enkephalin-Arg6-Phe7 + H2O
?
-
-
-
-
?
Met5-enkephalin-Arg6-Phe7 + H2O
?
-
-
-
-
?
Met5-enkephalin-Arg6-Phe7 + H2O
?
-
-
-
-
?
Met5-enkephalin-Arg6-Phe7 + H2O
?
-
-
-
-
?
N-dansyl-D-Ala-Gly-p-nitrophenyl-Ala-Gly + H2O
?
-
-
-
-
?
N-dansyl-D-Ala-Gly-p-nitrophenyl-Ala-Gly + H2O
?
-
-
-
-
?
neurokinin B + H2O
?
-
-
-
-
?
neurokinin B + H2O
?
-
-
-
?
neurokinin B + H2O
?
-
-
-
-
?
neurokinin B + H2O
?
-
-
-
-
?
neurotensin + H2O
?
-
-
-
-
?
neurotensin + H2O
?
-
-
-
?
neurotensin + H2O
?
-
-
-
-
?
neurotensin + H2O
?
-
cleaves at Pro10-Tyr11 and Tyr11-Ile12
-
-
?
neurotensin + H2O
?
-
-
-
-
?
neurotensin + H2O
?
-
-
-
-
?
neurotensin + H2O
?
-
-
-
-
?
oxytocin + H2O
?
-
-
-
-
?
oxytocin + H2O
?
-
-
-
-
?
oxytocin + H2O
?
-
-
-
-
?
physalaemin + H2O
?
-
-
-
-
?
physalaemin + H2O
?
-
-
-
-
?
physalaemin + H2O
?
-
-
-
-
?
physalaemin + H2O
?
-
-
-
-
?
pyroglutamyl-Leu-Asn-Phe-Thr-Pro-Asn-Trp-Gly-Thr-NH2 + H2O
pyroglutamyl-Leu-Asn + Phe-Thr-Pro-ASn-Trp-Gly-Thr-NH2
-
-
-
?
pyroglutamyl-Leu-Asn-Phe-Thr-Pro-Asn-Trp-Gly-Thr-NH2 + H2O
pyroglutamyl-Leu-Asn + Phe-Thr-Pro-ASn-Trp-Gly-Thr-NH2
-
-
-
?
pyroglutamyl-Leu-Asn-Phe-Thr-Pro-Asn-Trp-Gly-Thr-NH2 + H2O
pyroglutamyl-Leu-Asn + Phe-Thr-Pro-ASn-Trp-Gly-Thr-NH2
-
-
-
?
Substance P + H2O
?
Q9I7I4
85.8% degradation
-
-
?
Substance P + H2O
?
-
-
-
-
?
Substance P + H2O
?
-
-
-
?
Substance P + H2O
?
-
-
-
-
?
Substance P + H2O
?
-
cleaves at Gln6-Phe7, Phe7-Phe8, and Gly9-Leu10
-
-
?
Substance P + H2O
?
-
-
-
-
?
Substance P + H2O
?
-
-
-
-
?
Substance P + H2O
?
-
-
-
-
?
succinyl-Ala-Ala-Phe-4-methylcoumarin 7-amide + H2O
succinyl-Ala-Ala + Phe-4-methylcoumarin 7-amide
-
-
-
?
succinyl-Ala-Ala-Phe-4-methylcoumarin 7-amide + H2O
succinyl-Ala-Ala + Phe-4-methylcoumarin 7-amide
-
-
-
-
?
succinyl-Ala-Ala-Phe-4-methylcoumarin 7-amide + H2O
succinyl-Ala-Ala + Phe-4-methylcoumarin 7-amide
-
-
-
?
succinyl-Ala-Ala-Phe-4-methylcoumarin 7-amide + H2O
succinyl-Ala-Ala + Phe-4-methylcoumarin 7-amide
-
-
-
-
?
succinyl-Ala-Ala-Phe-4-methylcoumarin 7-amide + H2O
succinyl-Ala-Ala + Phe-4-methylcoumarin 7-amide
-
-
-
?
succinyl-Ala-Ala-Phe-7-amido-4-methylcoumarin + H2O
?
-
-
-
-
?
succinyl-Ala-Ala-Phe-7-amido-4-methylcoumarin + H2O
?
-
-
-
-
?
succinyl-Ala-Ala-Phe-7-amido-4-methylcoumarin + H2O
succinyl-Ala-Ala-Phe + 7-amino-4-methylcoumarin
-
-
-
?
succinyl-Ala-Ala-Phe-7-amido-4-methylcoumarin + H2O
succinyl-Ala-Ala-Phe + 7-amino-4-methylcoumarin
-
-
-
?
Tyr-D-Ala-Gly-Phe-Met + H2O
Tyr-D-Ala-Gly + Phe-Met
-
-
-
?
Tyr-D-Ala-Gly-Phe-Met + H2O
Tyr-D-Ala-Gly + Phe-Met
-
-
-
-
?
Tyr-D-Ala-Gly-Phe-Met-NH2 + H2O
Tyr-D-Ala-Gly + Phe-Met-NH2
-
-
-
-
?
Tyr-D-Ala-Gly-Phe-Met-NH2 + H2O
Tyr-D-Ala-Gly + Phe-Met-NH2
-
-
-
?
Tyr-D-Ala-Gly-Phe-Met-NH2 + H2O
Tyr-D-Ala-Gly + Phe-Met-NH2
-
-
-
-
?
Tyr-Gly-Gly-Phe-Met + H2O
Tyr-Gly-Gly + Phe-Met
-
i.e. methionine enkephalin
-
-
?
Tyr-Gly-Gly-Phe-Met + H2O
Tyr-Gly-Gly + Phe-Met
-
i.e. methionine enkephalin
-
-
?
Tyr-Gly-Gly-Phe-Met + H2O
Tyr-Gly-Gly + Phe-Met
-
i.e. methionine enkephalin
-
-
?
Tyr-Gly-Gly-Phe-Met + H2O
Tyr-Gly-Gly + Phe-Met
-
i.e. methionine enkephalin
-
-
?
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
?
-
-
the enzyme may play an important role as regulator of plasma-derived peptides in the nephron
-
-
?
additional information
?
-
-
-
-
-
?
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
?
-
-
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
?
-
-
neutral endopeptidase 24.11/CD10 suppresses the progression of ovarian carcinomas
-
-
?
additional information
?
-
-
no activity with angiotensin (1-7)
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?
additional information
?
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hydrolysis of polypeptides between hydrophobic residues
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?
additional information
?
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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
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?
additional information
?
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the enzyme degrades a wide range of peptide substrates, physiologically relevant peptides are such as enkephalins, tachykinins, and natriuretic peptides
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?
additional information
?
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the enzyme directly interacts with phosphatidylserine and cardiolipin but not with cholesterol
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?
additional information
?
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the enzyme has broader substrate specificity and is a peptidase capable of cleaving a variety of physiological peptides
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?
additional information
?
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human neprilysin-2 has a more restricted substrate specificity compared to human neprilysin with less activity against several vasoactive peptides
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?
additional information
?
-
activity measurement optimization using the synthetic fluorogenic peptide substrates, evaluation and kinetics, overview
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-
additional information
?
-
activity measurement optimization using the synthetic fluorogenic peptide substrates, evaluation and kinetics, overview
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?
additional information
?
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analysis of intact amyloid-beta peptides and their NEP cleavage products by mass spectrometry. 73% of amyloid-beta4-40, 31% of amyloid-beta4-42, 45% of amyloid-beta1-40, and 18% of amyloid-beta1-42 degradation resulting from NEP catalyzed hydrolysis. Amyloid-beta4-9/amyloid-beta1-9, amyloid-beta10-17, and amyloid-beta20-30 are the major enzymatic products
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-
-
additional information
?
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analysis of intact amyloid-beta peptides and their NEP cleavage products by mass spectrometry. 73% of amyloid-beta4-40, 31% of amyloid-beta4-42, 45% of amyloid-beta1-40, and 18% of amyloid-beta1-42 degradation resulting from NEP catalyzed hydrolysis. Amyloid-beta4-9/amyloid-beta1-9, amyloid-beta10-17, and amyloid-beta20-30 are the major enzymatic products
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?
additional information
?
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in vitro NEP proteolysis generates fragments that lack the ability to bind to the apelin receptor, NEP fully inactivates apelin
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-
additional information
?
-
in vitro NEP proteolysis generates fragments that lack the ability to bind to the apelin receptor, NEP fully inactivates apelin
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?
additional information
?
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murine amyloid-beta has a far lower propensity to aggregate than human amyloid-beta. Amyloid-beta degradation products formed during NEP incubation are identified by mass spectrometry, analysis of predominant NEP cleavage sites detected by mass spectrometry for human and murine amyloid-beta1-42 and amyloid-beta.4-15. In addition to the amyloid-beta4-9 fragment, di- and tetra-peptides amyloid-beta18-19 and amyloid-beta39-42 are also observed
-
-
-
additional information
?
-
-
murine amyloid-beta has a far lower propensity to aggregate than human amyloid-beta. Amyloid-beta degradation products formed during NEP incubation are identified by mass spectrometry, analysis of predominant NEP cleavage sites detected by mass spectrometry for human and murine amyloid-beta1-42 and amyloid-beta.4-15. In addition to the amyloid-beta4-9 fragment, di- and tetra-peptides amyloid-beta18-19 and amyloid-beta39-42 are also observed
-
-
-
additional information
?
-
murine amyloid-beta has a far lower propensity to aggregate than human amyloid-beta. Amyloid-beta degradation products formed during NEP incubation are identified by mass spectrometry, analysis of predominant NEP cleavage sites detected by mass spectrometry for human and murine amyloid-beta1-42 and amyloid-beta.4-15. In addition to the amyloid-beta4-9 fragment, di- and tetra-peptides amyloid-beta18-19 and amyloid-beta39-42 are also observed
-
-
?
additional information
?
-
-
murine amyloid-beta has a far lower propensity to aggregate than human amyloid-beta. Amyloid-beta degradation products formed during NEP incubation are identified by mass spectrometry, analysis of predominant NEP cleavage sites detected by mass spectrometry for human and murine amyloid-beta1-42 and amyloid-beta.4-15. In addition to the amyloid-beta4-9 fragment, di- and tetra-peptides amyloid-beta18-19 and amyloid-beta39-42 are also observed
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-
?
additional information
?
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-
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
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-
?
additional information
?
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-
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
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-
?
additional information
?
-
NEP degrades murine amyloid-beta faster than human amyloid-beta, observed with full-length amyloid-beta containing 40 or 42 amino acids (Abeta1-40 and Abeta1-42) and a truncated form (Abeta4-15), which contains one of the main NEP cleavage sites for amyloid-beta (between positions 9 and 10), harbours all three amino acid differences between murine and human amyloid-beta sequences, and is less prone to aggregation and thus might be a simpler model to investigate amyloid-beta biochemistry. Murine amyloid-beta has a far lower propensity to aggregate than human amyloid-beta. Amyloid-beta degradation products formed during NEP incubation are identified by mass spectrometry, analysis of predominant NEP cleavage sites detected by mass spectrometry for human and murine amyloid-beta1-42 and amyloid-beta.4-15. In addition to the amyloid-beta4-9 fragment, di- and tetra-peptides amyloid-beta18-19 and amyloid-beta39-42 are also observed
-
-
-
additional information
?
-
-
NEP degrades murine amyloid-beta faster than human amyloid-beta, observed with full-length amyloid-beta containing 40 or 42 amino acids (Abeta1-40 and Abeta1-42) and a truncated form (Abeta4-15), which contains one of the main NEP cleavage sites for amyloid-beta (between positions 9 and 10), harbours all three amino acid differences between murine and human amyloid-beta sequences, and is less prone to aggregation and thus might be a simpler model to investigate amyloid-beta biochemistry. Murine amyloid-beta has a far lower propensity to aggregate than human amyloid-beta. Amyloid-beta degradation products formed during NEP incubation are identified by mass spectrometry, analysis of predominant NEP cleavage sites detected by mass spectrometry for human and murine amyloid-beta1-42 and amyloid-beta.4-15. In addition to the amyloid-beta4-9 fragment, di- and tetra-peptides amyloid-beta18-19 and amyloid-beta39-42 are also observed
-
-
-
additional information
?
-
NEP degrades murine amyloid-beta faster than human amyloid-beta, observed with full-length amyloid-beta containing 40 or 42 amino acids (Abeta1-40 and Abeta1-42) and a truncated form (Abeta4-15), which contains one of the main NEP cleavage sites for amyloid-beta (between positions 9 and 10), harbours all three amino acid differences between murine and human amyloid-beta sequences, and is less prone to aggregation and thus might be a simpler model to investigate amyloid-beta biochemistry. Murine amyloid-beta has a far lower propensity to aggregate than human amyloid-beta. Amyloid-beta degradation products formed during NEP incubation are identified by mass spectrometry, analysis of predominant NEP cleavage sites detected by mass spectrometry for human and murine amyloid-beta1-42 and amyloid-beta.4-15. In addition to the amyloid-beta4-9 fragment, di- and tetra-peptides amyloid-beta18-19 and amyloid-beta39-42 are also observed
-
-
?
additional information
?
-
-
NEP degrades murine amyloid-beta faster than human amyloid-beta, observed with full-length amyloid-beta containing 40 or 42 amino acids (Abeta1-40 and Abeta1-42) and a truncated form (Abeta4-15), which contains one of the main NEP cleavage sites for amyloid-beta (between positions 9 and 10), harbours all three amino acid differences between murine and human amyloid-beta sequences, and is less prone to aggregation and thus might be a simpler model to investigate amyloid-beta biochemistry. Murine amyloid-beta has a far lower propensity to aggregate than human amyloid-beta. Amyloid-beta degradation products formed during NEP incubation are identified by mass spectrometry, analysis of predominant NEP cleavage sites detected by mass spectrometry for human and murine amyloid-beta1-42 and amyloid-beta.4-15. In addition to the amyloid-beta4-9 fragment, di- and tetra-peptides amyloid-beta18-19 and amyloid-beta39-42 are also observed
-
-
?
additional information
?
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-
the enzyme is the major inactivator of enkephalin in brain
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?
additional information
?
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-
the enzyme may participate in the regulation of blood pressure and water and sodium excretion through inactivation of kinins
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?
additional information
?
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-
the enzyme is the major inactivator of enkephalin in brain
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?
additional information
?
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-
the enzyme may participate in the regulation of blood pressure and water and sodium excretion through inactivation of kinins
-
-
?
additional information
?
-
-
in sepsis, the local concentration and action of adrenomedullin in tissue may be differentially regulated by NEP
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-
?
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
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-
?
additional information
?
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-
physiological role in metabolism of insect peptides at the synapse
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?
additional information
?
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-
-
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?
additional information
?
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-
could play an important role in the hydrolysis of neuropeptides
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?
additional information
?
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the enzyme may participate in the regulation of blood pressure and water and sodium excretion through inactivation of kinins
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-
?
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(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-(biphenyl-4-ylmethyl)-6-[4-[cyclohexyl(sulfanyl)methyl]phenyl]-4-oxo-5-sulfanylhexanoic acid
-
(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
-
-
(2R)-6-[4-[cyclohexyl(sulfanyl)methyl]phenyl]-4-oxo-5-sulfanyl-2-[4-(thiophen-3-yl)benzyl]hexanoic acid
-
(2S)-2-(biphenyl-4-ylmethyl)-6-[4-[cyclohexyl(sulfanyl)methyl]phenyl]-4-oxo-5-sulfanylhexanoic 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
-
-
(2S)-6-[4-[cyclohexyl(sulfanyl)methyl]phenyl]-4-oxo-5-sulfanyl-2-[4-(thiophen-3-yl)benzyl]hexanoic 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
2,3-Dimercaptopropan-1-ol
-
weak
2-(1-heptylcarbamoyl-cyclopentylmethyl)-4-methoxy-butyric acid tert-butyl ester
-
-
2-(4-bromobenzyl)-4-oxo-5-sulfanyl-6-[4-(2-sulfanylpropan-2-yl)phenyl]hexanoic acid
-
2-(4-bromobenzyl)-4-oxo-5-sulfanyl-6-[4-(3-sulfanylpentan-3-yl)phenyl]hexanoic acid
-
2-(4-bromobenzyl)-4-oxo-6-phenyl-5-sulfanylhexanoic acid
-
2-(4-bromobenzyl)-4-oxo-6-[4-[piperidin-4-yl(sulfanyl)methyl]phenyl]-5-sulfanylhexanoic acid
-
2-(4-bromobenzyl)-6-(4-bromophenyl)-4-oxo-5-sulfanylhexanoic acid
-
2-(4-bromobenzyl)-6-[4-(butan-2-yl)phenyl]-1-(morpholin-4-yl)-5-sulfanylhexane-1,4-dione
-
2-(4-bromobenzyl)-6-[4-(butan-2-yl)phenyl]-4-oxo-5-sulfanylhexanoic acid
-
2-(4-bromobenzyl)-6-[4-[2,3-dihydro-1H-inden-2-yl(sulfanyl)methyl]phenyl]-4-oxo-5-sulfanylhexanoic acid
-
2-(4-bromobenzyl)-6-[4-[cyclohexyl(sulfanyl)methyl]phenyl]-4-oxo-5-sulfanylhexanoic acid
-
2-(4-bromobenzyl)-6-[4-[cyclopentyl(sulfanyl)methyl]phenyl]-4-oxo-5-sulfanylhexanoic acid
-
2-(biphenyl-4-ylmethyl)-4-oxo-6-[4-[piperidin-4-yl(sulfanyl)methyl]phenyl]-5-sulfanylhexanoic acid
-
2-(biphenyl-4-ylmethyl)-6-[4-[2,3-dihydro-1H-inden-2-yl(sulfanyl)methyl]phenyl]-4-oxo-5-sulfanylhexanoic acid
-
2-(biphenyl-4-ylmethyl)-6-[4-[cyclohexyl(sulfanyl)methyl]phenyl]-4-oxo-5-sulfanylhexanoic acid
-
2-(biphenyl-4-ylmethyl)-6-[4-[cyclopentyl(sulfanyl)methyl]phenyl]-4-oxo-5-sulfanylhexanoic acid
-
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-benzyl-4-oxo-6-phenyl-5-sulfanylhexanoic acid
-
2-benzyl-6-(4-bromophenyl)-4-oxo-5-sulfanylhexanoic acid
-
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
-
-
6-(biphenyl-4-yl)-2-(4-bromobenzyl)-4-oxo-5-sulfanylhexanoic acid
-
6-[4-[(1-acetylpiperidin-4-yl)(sulfanyl)methyl]phenyl]-2-(4-bromobenzyl)-4-oxo-5-sulfanylhexanoic acid
-
6-[4-[(1-benzoylpiperidin-4-yl)(sulfanyl)methyl]phenyl]-2-(4-bromobenzyl)-4-oxo-5-sulfanylhexanoic acid
-
6-[4-[(1-benzylpiperidin-4-yl)(sulfanyl)methyl]phenyl]-2-(4-bromobenzyl)-4-oxo-5-sulfanylhexanoic acid
-
6-[4-[cyclohexyl(sulfanyl)methyl]phenyl]-4-oxo-5-sulfanyl-2-[4-(thiophen-3-yl)benzyl]hexanoic acid
-
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 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
-
atrial natriuretic factor
-
-
-
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
cis-4-[([1-[(2S)-2-carboxy-3-(2-methoxyethoxy)propyl]cyclopentyl]carbonyl)amino]cyclohexanecarboxylic acid
-
-
diisopropyl fluorophosphate
-
-
DL-[N-(3-mercapto-2-benzylpropanoyl)]glycine
-
following neprilysin inhibition, islet amyloid deposition and beta-cell apoptosis increase by 54 and 75%, respectively
fasidotrilat
fasidotrilat interacts with the Arg664 of hNEP with more consistent bidentate hydrogen bonding and with the His658 with monodentate hydrogen bonding
Hg2+
0.001-0.05 mM, modifies the recombinant enzyme conformation, and highly reduces the enzyme activity. Hg2+ incubation increases NEP protein levels, but does not change NEP mRNA levels nor the levels of the amyloid intracellular domain peptide, a protein fragment with transcriptional activity. The Hg2+-induced inhibition of the enzyme activity may be mediated by a conformational change resulting in reduced amyloid beta1-42 degradation
Insulin B chain
inhibits the activity with substrate N-(4-carboxy-1-oxobutyl)-L-alanyl-L-alanyl-N-(4-methoxy-2-naphthalenyl)-L-phenylalaninamide
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
MCB3937
bifunctional inhibitor of NEP and DPP-IV
MCB4241
bifunctional inhibitor of NEP and DPP-IV
N-(2-benzyl-3-sulfanylpropanoyl)glycine
-
synthetic NEP inhibitor
N-(2-benzyl-4-oxo-6-phenyl-5-sulfanylhexanoyl)-L-alanine
-
N-(2-benzyl-4-oxo-6-phenyl-5-sulfanylhexanoyl)-L-tryptophan
-
N-([1-[(2S)-2-carboxy-3-[[N2-(methylsulfonyl)-L-lysyl]amino]propyl]cyclopentyl]carbonyl)-L-tyrosine
-
-
N-phenethylphosphonyl-L-leucyl-L-tryptophan
N-[(2RS)-3-hydroxyaminocarbonyl-2-benzyl-1-oxopropyl]-Gly
-
-
N-[(2S)-3-phenyl-2-(sulfanylmethyl)propanoyl]-L-tryptophan
-
N-[1(R,S)-carboxy-2-phenylethyl]-Phe-p-aminobenzoate
-
-
N-[2-(4-bromobenzyl)-4-oxo-5-phenyl-5-sulfanylpentanoyl]-L-alanine
-
N-[2-(4-bromobenzyl)-4-oxo-5-sulfanylhexanoyl]-L-tryptophan
-
N-[2-(4-bromobenzyl)-4-oxo-6-phenyl-5-sulfanylhexanoyl]-L-alanine
-
N-[2-(4-bromobenzyl)-4-oxo-6-phenyl-5-sulfanylhexanoyl]-L-tryptophan
-
N-[2-(4-bromobenzyl)-6-methyl-4-oxo-5-sulfanyloctanoyl]-L-alanine
-
N-[2-(biphenyl-4-ylmethyl)-4-oxo-5-sulfanylhexanoyl]-L-alanine
-
N-[2-(biphenyl-4-ylmethyl)-4-oxo-6-phenyl-5-sulfanylhexanoyl]-L-alanine
-
N-[2-(biphenyl-4-ylmethyl)-6-methyl-4-oxo-5-sulfanyloctanoyl]-L-alanine
-
N-[2-benzyl-6-(4-bromophenyl)-4-oxo-5-sulfanylhexanoyl]-L-leucine
-
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
-
-
sacubitrilat
LBQ657, the inhibitor is bound to the active site of NEP by an intricate network of interactions that involves all functional groups of the compound giving rise to the high inhibitory potency. The catalytic zinc atom of NEP is ligated by the side chains of residues His583, His587, and Glu646 with the fourth coordination provided by the carboxylate oxygen adjacent to the P1 methyl of the compound, the backbone amide of LBQ657 forms H-bonding interactions with the side chains of Asn542 and Arg717. Enzyme active site binding structure, interaction, and inhibition mechanism, modelling, overview. All of the molecular interactions between LBQ657 and the enzyme are noncovalent, in line with a reversible inhibition mode
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
tert-butyl 2-([1-[(5-benzyl-1,3,4-thiadiazol-2-yl)carbamoyl]cyclopentyl]methyl)-4-methoxybutanoate
-
-
tris(2-carboxyethyl)phosphine
TCEP, strong inhibition
U46619
a thromboxane mimetic
1,10-phenanthroline
-
-
2-mercaptoethanol
-
-
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
-
candoxatrilat
-
-
candoxatrilat
-
application restores vagal reflex bradycardia in old rats to levels similar to those in young neutral endopeptidase inhibitor-treated rats
dithiothreitol
-
-
EDTA
-
-
L-Cys
-
-
Leu5-enkephalin
-
-
Leu5-enkephalin
-
hydrolysis of succinyl-Ala-Ala-Phe-4-methylcoumarin 7-amide
Met5-enkephalin
-
-
Met5-enkephalin
-
hydrolysis of succinyl-Ala-Ala-Phe-4-methylcoumarin 7-amide
N-phenethylphosphonyl-L-leucyl-L-tryptophan
NPLT, synthesis of the phosphoramidon derivative with enhanced permeability into the skin that shows inability to inhibit type I and type IV collagenase, but inhibits fibroblast elastase
N-phenethylphosphonyl-L-leucyl-L-tryptophan
NPLT, synthesis of the phosphoramidon derivative with enhanced permeability into the skin that shows inability to inhibit type I and type IV collagenase, but inhibits fibroblast elastase
N-phenethylphosphonyl-L-leucyl-L-tryptophan
NPLT, synthesis of the phosphoramidon derivative with enhanced permeability into the skin that shows inability to inhibit type I and type IV collagenase, but inhibits fibroblast elastase
NaCl
-
brain enzyme; lung enzyme
NaCl
-
no inhibition of the enzyme from brain and kidney
phosphoramidon
-
-
phosphoramidon
a typical inhibitor for metalloproteinase
phosphoramidon
strong, consistent interactions with Arg664, Glu531 and His658 of hNEP
phosphoramidon
the inhibitor induces a dramatic increase in amyloid-beta peptide levels
phosphoramidon
a typical inhibitor for metalloproteinase
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
-
the inhibitor induces a dramatic increase in amyloid-beta peptide levels
phosphoramidon
a typical inhibitor for metalloproteinase
phosphoramidon
-
synthetic NEP inhibitor
thiol
-
kidney enzyme; lung enzyme
thiol
-
intestine enzyme; kidney enzyme
thiorphan
-
-
thiorphan
complete inhibition
thiorphan
Arg49 and Arg664 act to support the ligand binding in NEP
thiorphan
the inhibitor induces a dramatic increase in amyloid-beta peptide levels
thiorphan
-
thiorphan eliminates proteolysis of the alpha-subunit
thiorphan
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
-
the inhibitor induces a dramatic increase in amyloid-beta peptide levels
thiorphan
a NEP-specific inhibitor
thiorphan-NH2
-
-
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
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
no inhibition by 4-(2-butylbenzyl)-5-(4-hydroxybenzyl)-1-[1-(2-[[6-(4-hydroxybenzyl)-2,3-dioxopiperazin-1-yl]methyl]pyrrolidin-1-yl)-3-(naphthalen-2-yl)propan-2-yl]piperazine-2,3-dione and 4-(cyclopentylmethyl)-5-(4-hydroxybenzyl)-1-[1-(2-[[6-(4-hydroxybenzyl)-2,3-dioxopiperazin-1-yl]methyl]pyrrolidin-1-yl)-3-(naphthalen-2-yl)propan-2-yl]piperazine-2,3-dione
-
additional information
-
no inhibition by 4-(2-butylbenzyl)-5-(4-hydroxybenzyl)-1-[1-(2-[[6-(4-hydroxybenzyl)-2,3-dioxopiperazin-1-yl]methyl]pyrrolidin-1-yl)-3-(naphthalen-2-yl)propan-2-yl]piperazine-2,3-dione and 4-(cyclopentylmethyl)-5-(4-hydroxybenzyl)-1-[1-(2-[[6-(4-hydroxybenzyl)-2,3-dioxopiperazin-1-yl]methyl]pyrrolidin-1-yl)-3-(naphthalen-2-yl)propan-2-yl]piperazine-2,3-dione
-
additional information
desing of neprilysin inhibitors containing an alpha-mercaptoketone HSC(R1R2)CO group, as zinc ligand, substituted alpha-mercaptoketones are specific neprilysin inhibitors, optimization of the enzyme-inhibitor interactions within the S1 subsite, overview. Role of the size of the inhibitor which interacts with the S1, S1', or S2' domain of the enzyme and the nature of the substituents R1, and R2 of the mercaptoketone group in inhibitor potency. Introduction of a cyclohexyl chain in R1, R2 position and a (3-thiophen)benzyl group in position R3 yields to the most potent inhibitor of this series with a Ki value
-
additional information
structure-activity relationship studies. No or poor inhibition by 4-(2-aminoethyl)benzylsulfonyl fluoride (AEBSF), and Nalpha-tosyl-l-lysyl chloromethylketone (TLCK), and iodoacetamide
-
additional information
molecular docking studies, overview. For substrate and inhibitor binding, Arg664 and Zn697 are identified as the most conserved residues
-
additional information
-
molecular docking studies, overview. For substrate and inhibitor binding, Arg664 and Zn697 are identified as the most conserved residues
-
additional information
-
application of aldosterone, atrial natriuretic peptide, asymmetric dimethylarginine, and angiotensin peptides fail to cause down-regulation of renal neprilysin expression in vitro
-
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0.0068 - 0.0224
(7-methoxycoumarin-4-yl)acetyl-Arg-Pro-Pro-Gly-Phe-Ser-Ala-Phe-Lys(2,4-dinitrophenyl)
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
0.024
alpha-endorphin
wild-type enzyme, pH and temperature not specified in the publication
0.135
alpha-neoendorphin
-
-
0.014 - 0.104
amyloid beta peptide1-40
-
0.0086
angiotensin
wild-type enzyme, pH and temperature not specified in the publication
0.0004 - 34.1
angiotensin I
0.179
angiotensin II
-
37°C, pH 7.4
0.1114
angiotensin(1-9)
-
37°C, pH 7.4
0.0062
Arg-vasopressin
wild-type enzyme, pH and temperature not specified in the publication
0.25
benzyloxycarbonyl-Ala-Gly-Leu-Ala
-
-
0.00654
beta-endorphin
-
-
0.296
cholecystokinin-8
-
-
0.07 - 2.137
D-Ala2-Leu5-enkephalin
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
-
-
0.0082
dynorphin A-17
-
-
0.053
endothelin-1
wild-type enzyme, pH and temperature not specified in the publication
0.013
gamma-endorphin
wild-type enzyme, pH and temperature not specified in the publication
0.15
gastri-releasing peptide
wild-type enzyme, pH and temperature not specified in the publication
0.049 - 0.068
gastrin G-17
0.024
GLP-1
wild-type enzyme, pH and temperature not specified in the publication
-
0.025
glucagon
wild-type enzyme, pH and temperature not specified in the publication
0.59
glutaryl-Ala-Ala-Phe-2-naphthylamide
-
-
0.12
glutaryl-Ala-Ala-Phe-4-methoxy-2-naphthylamine
-
-
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 - 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
0.022 - 0.1
Met-enkephalin
0.41
Met-enkephalin amide
-
-
0.062
Met5-enkephalin
-
-
0.039
Met5-enkephalin-Arg6
-
-
0.05
Met5-enkephalin-Arg6Phe7
-
-
0.011 - 0.087
N-(4-carboxy-1-oxobutyl)-L-alanyl-L-alanyl-N-(4-methoxy-2-naphthalenyl)-L-phenylalaninamide
0.42
N-(4-carboxybutanoyl)-L-alanyl-L-alanyl-N-(4-methoxynaphthalen-2-yl)-L-phenylalaninamide
-
-
0.0408
N-2-aminobenzoyl-rGV-N-(2,4-dinitrophenyl)ethylenediamine
-
-
0.13
N-benzyoxycarbonyl-Gly-Gly-Leu 2-naphthylamide
-
-
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
-
-
0.0093
Neurokinin A
wild-type enzyme, pH and temperature not specified in the publication
0.022
neurokinin B
wild-type enzyme, pH and temperature not specified in the publication
0.016 - 0.078
neurotensin
0.02
nociceptin
wild-type enzyme, pH and temperature not specified in the publication
0.0074
somatostatin 14
wild-type enzyme, pH and temperature not specified in the publication
0.031
somatostatin 28
wild-type enzyme, pH and temperature not specified in the publication
0.043 - 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 - 0.019
Tyr-D-Ala-Gly-Phe-Leu
0.013
Tyr-D-Ala-Gly-Phe-Met
-
-
0.061 - 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
-
-
additional information
additional information
Michaelis-Menten profiles and steady-state kinetic parameters for cleavage of amyloid beta peptide1-40 and off-target peptide by wild-type and mutant enzymes, overview
-
0.0068
(7-methoxycoumarin-4-yl)acetyl-Arg-Pro-Pro-Gly-Phe-Ser-Ala-Phe-Lys(2,4-dinitrophenyl)
pH 7.5, 37°C
0.0224
(7-methoxycoumarin-4-yl)acetyl-Arg-Pro-Pro-Gly-Phe-Ser-Ala-Phe-Lys(2,4-dinitrophenyl)
pH 7.5, 37°C, in presence of activating K49-P1-20
0.014
amyloid beta peptide1-40
mutant G399V/G714K, pH and temperature not specified in the publication
-
0.042
amyloid beta peptide1-40
mutant G714K, pH and temperature not specified in the publication
-
0.055
amyloid beta peptide1-40
mutant G399V, pH and temperature not specified in the publication
-
0.104
amyloid beta peptide1-40
wild-type enzyme, pH and temperature not specified in the publication
-
0.0004
angiotensin I
-
-
34.1
angiotensin I
-
37°C, pH 7.4
0.005
bradykinin
-
-
0.032
bradykinin
wild-type enzyme, pH and temperature not specified in the publication
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
0.049
gastrin G-17
-
sulfated
0.068
gastrin G-17
-
unsulfated
0.074
Leu-enkephalin
-
-
0.755
Luteinizing hormone-releasing hormone
-
-
0.755
Luteinizing hormone-releasing hormone
-
-
0.022
Met-enkephalin
-
-
0.011
N-(4-carboxy-1-oxobutyl)-L-alanyl-L-alanyl-N-(4-methoxy-2-naphthalenyl)-L-phenylalaninamide
pH 6.5, 37°C, mutant NEPS546A
0.051
N-(4-carboxy-1-oxobutyl)-L-alanyl-L-alanyl-N-(4-methoxy-2-naphthalenyl)-L-phenylalaninamide
pH 6.5, 37°C, wild-type enzyme and mutant NEPF563V
0.073
N-(4-carboxy-1-oxobutyl)-L-alanyl-L-alanyl-N-(4-methoxy-2-naphthalenyl)-L-phenylalaninamide
pH 6.5, 37°C, mutant NEPS546T
0.074
N-(4-carboxy-1-oxobutyl)-L-alanyl-L-alanyl-N-(4-methoxy-2-naphthalenyl)-L-phenylalaninamide
pH 6.5, 37°C, mutant NEPS546E
0.081
N-(4-carboxy-1-oxobutyl)-L-alanyl-L-alanyl-N-(4-methoxy-2-naphthalenyl)-L-phenylalaninamide
pH 6.5, 37°C, mutant NEPF563L
0.083
N-(4-carboxy-1-oxobutyl)-L-alanyl-L-alanyl-N-(4-methoxy-2-naphthalenyl)-L-phenylalaninamide
pH 6.5, 37°C, mutant NEPF563I
0.087
N-(4-carboxy-1-oxobutyl)-L-alanyl-L-alanyl-N-(4-methoxy-2-naphthalenyl)-L-phenylalaninamide
pH 6.5, 37°C, mutant NEPF563M
0.016
neurotensin
wild-type enzyme, pH and temperature not specified in the publication
0.01
Substance P
-
-
0.016
Substance P
wild-type enzyme, pH and temperature not specified in the publication
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
-
-
0.018
Tyr-D-Ala-Gly-Phe-Leu
-
-
0.019
Tyr-D-Ala-Gly-Phe-Leu
-
-
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
-
-
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0.0000013
(2(R,S)-2-sulfanyl-2-benzyl)acetyl-Ala-Pro
Homo sapiens
-
-
0.0000022
(2(R,S)-2-sulfanyl-2-benzyl)acetyl-Leu-Tyr
Homo sapiens
-
-
0.0000023
(2(R,S)-2-sulfanyl-2-benzyl)acetyl-Phe-Ala
Homo sapiens
-
-
0.0000029
(2(R,S)-2-sulfanyl-2-benzyl)acetyl-Phe-Tyr
Homo sapiens
-
-
0.0000014
(2(R,S)-2-sulfanyl-2-isopropyl)acetyl-Ile-Tyr
Homo sapiens
-
-
0.000036
(2R)-2-(biphenyl-4-ylmethyl)-6-[4-[cyclohexyl(sulfanyl)methyl]phenyl]-4-oxo-5-sulfanylhexanoic acid
Homo sapiens
pH and temperature not specified in the publication
0.00000237
(2R)-2-([1-[(5-ethyl-1,3,4-thiadiazol-2-yl)carbamoyl]cyclopentyl]methyl)pentanoic acid
Canis lupus familiaris
-
-
0.0000019
(2R)-2-[(1-[[(1S)-1-carboxy-2-(3-phenyl-1,2,4-oxadiazol-5-yl)ethyl]carbamoyl]cyclopentyl)methyl]-5-oxopentanoic acid
Homo sapiens
-
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
Homo sapiens
-
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
Homo sapiens
-
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
Homo sapiens
-
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
Homo sapiens
-
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
Homo sapiens
-
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
Homo sapiens
-
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
Homo sapiens
-
pH and temperature not specified in the publication
0.0000003 - 0.000005
(2R)-2-[[1-([(1S)-1-carboxy-2-[5-(4-chlorophenyl)-1,3-oxazol-2-yl]ethyl]carbamoyl)cyclopentyl]methyl]-5-oxopentanoic acid
0.000061
(2R)-6-[4-[cyclohexyl(sulfanyl)methyl]phenyl]-4-oxo-5-sulfanyl-2-[4-(thiophen-3-yl)benzyl]hexanoic acid
Homo sapiens
pH and temperature not specified in the publication
0.0000042
(2S)-2-(biphenyl-4-ylmethyl)-6-[4-[cyclohexyl(sulfanyl)methyl]phenyl]-4-oxo-5-sulfanylhexanoic acid
Homo sapiens
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
Canis lupus familiaris
-
-
0.000000009
(2S)-2-[(1-[[3-(4-chlorophenyl)propyl]carbamoyl]cyclopentyl)methyl]-4-methoxybutanoic acid
Canis lupus familiaris
-
-
0.0000002
(2S)-2-[(1-[[3-(4-fluorophenyl)propyl]carbamoyl]cyclopentyl)methyl]-4-methoxybutanoic acid
Canis lupus familiaris
-
-
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)
Homo sapiens
-
pH and temperature not specified in the publication
0.0000426
(2S)-4-methoxy-2-([1-[(1-methyl-2-phenylethyl)carbamoyl]cyclopentyl]methyl)butanoic acid
Canis lupus familiaris
-
-
0.0000008
(2S)-4-methoxy-2-[(1-[[(1R,2S)-2-(4-methoxyphenyl)cyclopropyl]carbamoyl]cyclopentyl)methyl]butanoic acid
Canis lupus familiaris
-
-
0.000002
(2S)-6-[4-[cyclohexyl(sulfanyl)methyl]phenyl]-4-oxo-5-sulfanyl-2-[4-(thiophen-3-yl)benzyl]hexanoic acid
Homo sapiens
pH and temperature not specified in the publication
0.0000008
2-(1-heptylcarbamoyl-cyclopentylmethyl)-4-methoxy-butyric acid tert-butyl ester
Canis lupus familiaris
-
-
0.00047
2-(4-bromobenzyl)-4-oxo-5-sulfanyl-6-[4-(2-sulfanylpropan-2-yl)phenyl]hexanoic acid
Homo sapiens
pH and temperature not specified in the publication
0.000086
2-(4-bromobenzyl)-4-oxo-5-sulfanyl-6-[4-(3-sulfanylpentan-3-yl)phenyl]hexanoic acid
Homo sapiens
pH and temperature not specified in the publication
0.00005
2-(4-bromobenzyl)-4-oxo-6-phenyl-5-sulfanylhexanoic acid
Homo sapiens
pH and temperature not specified in the publication
0.000054
2-(4-bromobenzyl)-4-oxo-6-[4-[piperidin-4-yl(sulfanyl)methyl]phenyl]-5-sulfanylhexanoic acid
Homo sapiens
pH and temperature not specified in the publication
0.00026
2-(4-bromobenzyl)-6-(4-bromophenyl)-4-oxo-5-sulfanylhexanoic acid
Homo sapiens
pH and temperature not specified in the publication
0.00165
2-(4-bromobenzyl)-6-[4-(butan-2-yl)phenyl]-1-(morpholin-4-yl)-5-sulfanylhexane-1,4-dione
Homo sapiens
pH and temperature not specified in the publication
0.00002
2-(4-bromobenzyl)-6-[4-(butan-2-yl)phenyl]-4-oxo-5-sulfanylhexanoic acid
Homo sapiens
pH and temperature not specified in the publication
0.000036
2-(4-bromobenzyl)-6-[4-[2,3-dihydro-1H-inden-2-yl(sulfanyl)methyl]phenyl]-4-oxo-5-sulfanylhexanoic acid
Homo sapiens
pH and temperature not specified in the publication
0.000032
2-(4-bromobenzyl)-6-[4-[cyclohexyl(sulfanyl)methyl]phenyl]-4-oxo-5-sulfanylhexanoic acid
Homo sapiens
pH and temperature not specified in the publication
0.000052
2-(4-bromobenzyl)-6-[4-[cyclopentyl(sulfanyl)methyl]phenyl]-4-oxo-5-sulfanylhexanoic acid
Homo sapiens
pH and temperature not specified in the publication
0.000061
2-(biphenyl-4-ylmethyl)-4-oxo-6-[4-[piperidin-4-yl(sulfanyl)methyl]phenyl]-5-sulfanylhexanoic acid
Homo sapiens
pH and temperature not specified in the publication
0.000026
2-(biphenyl-4-ylmethyl)-6-[4-[2,3-dihydro-1H-inden-2-yl(sulfanyl)methyl]phenyl]-4-oxo-5-sulfanylhexanoic acid
Homo sapiens
pH and temperature not specified in the publication
0.000009
2-(biphenyl-4-ylmethyl)-6-[4-[cyclohexyl(sulfanyl)methyl]phenyl]-4-oxo-5-sulfanylhexanoic acid
Homo sapiens
pH and temperature not specified in the publication
0.000029
2-(biphenyl-4-ylmethyl)-6-[4-[cyclopentyl(sulfanyl)methyl]phenyl]-4-oxo-5-sulfanylhexanoic acid
Homo sapiens
pH and temperature not specified in the publication
0.0015
2-([1-[(1,3-benzodioxol-5-ylmethyl)carbamoyl]cyclopentyl]methyl)pentanoic acid
Canis lupus familiaris
-
IC50: 1500 nM
0.000384
2-([1-[(1-benzyl-2-hydroxyethyl)carbamoyl]cyclopentyl]methyl)pentanoic acid
Canis lupus familiaris
-
IC50: 384 nM
0.000313
2-([1-[(1-benzyl-6-oxo-1,6-dihydropyridin-3-yl)carbamoyl]cyclopentyl]methyl)pentanoic acid
Canis lupus familiaris
-
IC50: 313 nM
0.000082
2-([1-[(1-ethyl-1H-1,2,3-triazol-4-yl)carbamoyl]cyclopentyl]methyl)pentanoic acid
Canis lupus familiaris
-
IC50: 82 nM
0.00171
2-([1-[(3-ethylpyridin-2-yl)carbamoyl]cyclopentyl]methyl)pentanoic acid
Canis lupus familiaris
-
IC50: 1710 nM
0.000096
2-([1-[(4-benzylpyridin-2-yl)carbamoyl]cyclopentyl]methyl)pentanoic acid
Canis lupus familiaris
-
IC50: 96 nM
0.000184
2-([1-[(4-butylpyridin-2-yl)carbamoyl]cyclopentyl]methyl)pentanoic acid
Canis lupus familiaris
-
IC50: 184 nM
0.00015
2-([1-[(4-carbamoylcyclohexyl)carbamoyl]cyclopentyl]methyl)pentanoic acid
Canis lupus familiaris
-
IC50: 150 nM
0.00003
2-([1-[(5-benzyl-1,3,4-thiadiazol-2-yl)carbamoyl]cyclopentyl]methyl)pentanoic acid
Canis lupus familiaris
-
IC50: 30 nM
0.000046
2-([1-[(5-ethyl-1,3,4-thiadiazol-2-yl)carbamoyl]cyclopentyl]methyl)-4-phenylbutanoic acid
Canis lupus familiaris
-
IC50: 46 nM
0.00012
2-([1-[(5-ethyl-1,3,4-thiadiazol-2-yl)carbamoyl]cyclopentyl]methyl)-5-methylhexanoic acid
Canis lupus familiaris
-
IC50: 120 nM
0.000084
2-([1-[(5-ethyl-1,3,4-thiadiazol-2-yl)carbamoyl]cyclopentyl]methyl)hexanoic acid
Canis lupus familiaris
-
IC50: 84 nM
0.00006
2-([1-[(5-ethyl-1,3,4-thiadiazol-2-yl)carbamoyl]cyclopentyl]methyl)pentanoic acid
Canis lupus familiaris
-
IC50: 60 nM
0.000176
2-([1-[(5-methyl-1,3,4-thiadiazol-2-yl)carbamoyl]cyclopentyl]methyl)pentanoic acid
Canis lupus familiaris
-
IC50: 176 nM
0.000283
2-([1-[(5-phenyl-1,3,4-thiadiazol-2-yl)carbamoyl]cyclopentyl]methyl)pentanoic acid
Canis lupus familiaris
-
IC50: 283 nM
0.000374
2-([1-[(6-methoxypyridazin-3-yl)carbamoyl]cyclopentyl]methyl)pentanoic acid
Canis lupus familiaris
-
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
Canis lupus familiaris
-
IC50: 1139 nM
0.00014
2-benzyl-4-oxo-6-phenyl-5-sulfanylhexanoic acid
Homo sapiens
pH and temperature not specified in the publication
0.00175
2-benzyl-6-(4-bromophenyl)-4-oxo-5-sulfanylhexanoic acid
Homo sapiens
pH and temperature not specified in the publication
0.0000065
2-methoxymethyl-3-[1-(trans-2-phenyl-cyclopropylcarbamoyl)-cyclopentyl]-propionic acid tert-butyl ester
Canis lupus familiaris
-
-
0.00053
2-[(1-[[(1R)-1-phenylethyl]carbamoyl]cyclopentyl)methyl]pentanoic acid
Canis lupus familiaris
-
IC50: 530 nM
0.000297
2-[(1-[[(1R)-3-(dimethylcarbamoyl)cyclohexyl]carbamoyl]cyclopentyl)methyl]pentanoic acid
Canis lupus familiaris
-
IC50: 297 nM
0.000195
2-[(1-[[(1R,2R)-2-benzylcyclohexyl]carbamoyl]cyclopentyl)methyl]pentanoic acid
Canis lupus familiaris
-
IC50: 195 nM
0.00089
2-[(1-[[(1R,2S)-2-propylcyclohexyl]carbamoyl]cyclopentyl)methyl]pentanoic acid
Canis lupus familiaris
-
IC50: 890 nM
0.00106
2-[(1-[[(3R)-1-benzylpyrrolidin-3-yl]carbamoyl]cyclopentyl)methyl]pentanoic acid
Canis lupus familiaris
-
IC50: 1060 nM
0.000213
2-[(1-[[(3R)-1-carbamoylpyrrolidin-3-yl]carbamoyl]cyclopentyl)methyl]pentanoic acid
Canis lupus familiaris
-
IC50: 213 nM
0.0007
2-[(1-[[(5-methyl-1,3,4-thiadiazol-2-yl)methyl]carbamoyl]cyclopentyl)methyl]pentanoic acid
Canis lupus familiaris
-
IC50: 700 nM
0.00171
2-[(1-[[1-(hydroxymethyl)cyclopentyl]carbamoyl]cyclopentyl)methyl]pentanoic acid
Canis lupus familiaris
-
IC50: 1710 nM
0.000096
2-[(1-[[2-(hydroxymethyl)-2,3-dihydro-1H-inden-2-yl]carbamoyl]cyclopentyl)methyl]pentanoic acid
Canis lupus familiaris
-
IC50: 96 nM
0.00037
2-[(1-[[4-(dimethylcarbamoyl)cyclohexyl]carbamoyl]cyclopentyl)methyl]pentanoic acid
Canis lupus familiaris
-
IC50: 370 nM
0.000124
2-[(1-[[5-(2-methylpropyl)-1,3,4-thiadiazol-2-yl]carbamoyl]cyclopentyl)methyl]pentanoic acid
Canis lupus familiaris
-
IC50: 124 nM
0.000038
2-[(1-[[5-(cyclopropylmethyl)-1,3,4-thiadiazol-2-yl]carbamoyl]cyclopentyl)methyl]pentanoic acid
Canis lupus familiaris
-
IC50: 38 nM
0.0000011
2-[1-(2-hydroxymethyl-indan-2-ylcarbamoyl)-cyclopentylmethyl]-4-methoxy-butyric acid tert-butyl ester
Canis lupus familiaris
-
-
0.0000017
2-[1-(4-butyl-pyridin-2-ylcarbamoyl)-cyclopentylmethyl]-4-methoxybutyric acid benzyl ester
Canis lupus familiaris
-
-
0.000006
2-[1-(5-ethyl-[1,3,4]thiadiazol-2-ylcarbamoyl)-cyclopentylmethyl]-pentanoic acid
Canis lupus familiaris
-
-
0.0000021
2-[1-[2-(trans-4-chlorophenyl)-cyclopropylcarbamoyl]-cyclopentylmethyl]-4-methoxy-butyric acid tert-butyl ester
Canis lupus familiaris
-
-
0.0000002
2-[1-[3-(4-chloro-phenyl)-propylcarbamoyl]-cyclopentylmethyl]-4-methoxy-butyric acid tert-butyl ester
Canis lupus familiaris
-
-
0.0000015
2-[1-[3-(4-fluoro-phenyl)-propylcarbamoyl]-cyclopentylmethyl]-4-methoxy-butyric acid tert-butyl ester
Canis lupus familiaris
-
-
0.000377
2-[[1-(1,3,4-thiadiazol-2-ylcarbamoyl)cyclopentyl]methyl]pentanoic acid
Canis lupus familiaris
-
IC50: 377 nM
0.000313
2-[[1-(2,3-dihydro-1H-inden-2-ylcarbamoyl)cyclopentyl]methyl]pentanoic acid
Canis lupus familiaris
-
IC50: 313 nM
0.0031
2-[[1-(5-benzyl-1,3,4-oxadiazol-2-yl)cyclopentyl]methyl]pentanoic acid
Canis lupus familiaris
-
IC50: 3100 nM
0.0015
2-[[1-(pyridin-2-ylcarbamoyl)cyclopentyl]methyl]pentanoic acid
Canis lupus familiaris
-
IC50: 1500 nM
0.000237
3-[1-[(5-ethyl-1,3,4-thiadiazol-2-yl)carbamoyl]cyclopentyl]propanoic acid
Canis lupus familiaris
-
IC50: 237 nM
0.000002
3-[1-[2-(trans-4-chlorophenyl)-cyclopropylcarbamoyl]-cyclopentyl]-2-methoxymethyl-propionic acid tert-butyl ester
Canis lupus familiaris
-
-
0.00005
4-methoxy-2-(1-phenethylcarbamoyl-cyclopentylmethyl)-butyric acid benzyl ester
Canis lupus familiaris
-
-
0.0000035
4-methoxy-2-[1-(3-phenyl-propylcarbamoyl)-cyclopentylmethyl]-butyric acid tert-butyl ester
Canis lupus familiaris
-
-
0.000001
4-methoxy-2-[1-(trans-2-pentyl-cyclopropylcarbamoyl)-cyclopentylmethyl]-butyric acid tert-butyl ester
Canis lupus familiaris
-
-
0.00001
4-methoxy-2-[1-(trans-2-phenyl-cyclopropylcarbamoyl)-cyclopentylmethyl]-butyric acid tert-butyl ester
Canis lupus familiaris
-
-
0.000004
4-methoxy-2-[1-[(trans-2-(4-fluorophenyl)-cyclopropylcarbamoyl)]-cyclopentylmethyl]-butyric acid tert-butyl ester
Canis lupus familiaris
-
-
0.0000008
4-methoxy-2-[1-[(trans-2-(4-methoxy-phenyl)-cyclopropylcarbamoyl)]-cyclopentylmethyl]-butyric acid tert-butyl ester
Canis lupus familiaris
-
-
0.0000035
4-methoxy-2-[1-[2-(4-methoxy-phenoxy)-ethylcarbamoyl]-cyclopentylmethyl]-butyric acid tert-butyl ester
Canis lupus familiaris
-
-
0.0000369
4-methoxy-2-[1-[2-(4-methoxy-phenyl)-ethylcarbamoyl]-cyclopentylmethyl]-butyric acid tert-butyl ester
Canis lupus familiaris
-
-
0.0000002
4-methoxy-2-[1-[3-(4-methoxy-phenyl)-propylcarbamoyl]-cyclopentylmethyl]-butyric acid tert-butyl ester
Canis lupus familiaris
-
-
0.000252
6-(biphenyl-4-yl)-2-(4-bromobenzyl)-4-oxo-5-sulfanylhexanoic acid
Homo sapiens
pH and temperature not specified in the publication
0.000095
6-[4-[(1-acetylpiperidin-4-yl)(sulfanyl)methyl]phenyl]-2-(4-bromobenzyl)-4-oxo-5-sulfanylhexanoic acid
Homo sapiens
pH and temperature not specified in the publication
0.000049
6-[4-[(1-benzoylpiperidin-4-yl)(sulfanyl)methyl]phenyl]-2-(4-bromobenzyl)-4-oxo-5-sulfanylhexanoic acid
Homo sapiens
pH and temperature not specified in the publication
0.000054
6-[4-[(1-benzylpiperidin-4-yl)(sulfanyl)methyl]phenyl]-2-(4-bromobenzyl)-4-oxo-5-sulfanylhexanoic acid
Homo sapiens
pH and temperature not specified in the publication
0.0000046
6-[4-[cyclohexyl(sulfanyl)methyl]phenyl]-4-oxo-5-sulfanyl-2-[4-(thiophen-3-yl)benzyl]hexanoic acid
Homo sapiens
pH and temperature not specified in the publication
0.0000078
cis-4-[([1-[(2S)-2-carboxy-3-(2-methoxyethoxy)propyl]cyclopentyl]carbonyl)amino]cyclohexanecarboxylic acid
Homo sapiens
-
pH and temperature not specified in the publication
0.00045
MCB3937
Homo sapiens
-
0.0006
MCB4241
Homo sapiens
-
0.000095
N-(2-benzyl-4-oxo-6-phenyl-5-sulfanylhexanoyl)-L-alanine
Homo sapiens
pH and temperature not specified in the publication
0.000018
N-(2-benzyl-4-oxo-6-phenyl-5-sulfanylhexanoyl)-L-tryptophan
Homo sapiens
pH and temperature not specified in the publication
0.0000006
N-([1-[(2S)-2-carboxy-3-[[N2-(methylsulfonyl)-L-lysyl]amino]propyl]cyclopentyl]carbonyl)-L-tyrosine
Homo sapiens
-
pH and temperature not specified in the publication
0.000008
N-phenethylphosphonyl-L-leucyl-L-tryptophan
Homo sapiens
pH not specified in the publication, 37°C
0.000022
N-[2-(4-bromobenzyl)-4-oxo-5-phenyl-5-sulfanylpentanoyl]-L-alanine
Homo sapiens
pH and temperature not specified in the publication
0.000162
N-[2-(4-bromobenzyl)-4-oxo-5-sulfanylhexanoyl]-L-tryptophan
Homo sapiens
pH and temperature not specified in the publication
0.000078
N-[2-(4-bromobenzyl)-4-oxo-6-phenyl-5-sulfanylhexanoyl]-L-alanine
Homo sapiens
pH and temperature not specified in the publication
0.00003
N-[2-(4-bromobenzyl)-4-oxo-6-phenyl-5-sulfanylhexanoyl]-L-tryptophan
Homo sapiens
pH and temperature not specified in the publication
0.000007
N-[2-(4-bromobenzyl)-6-methyl-4-oxo-5-sulfanyloctanoyl]-L-alanine
Homo sapiens
pH and temperature not specified in the publication
0.00004
N-[2-(biphenyl-4-ylmethyl)-4-oxo-5-sulfanylhexanoyl]-L-alanine
Homo sapiens
pH and temperature not specified in the publication
0.000046
N-[2-(biphenyl-4-ylmethyl)-4-oxo-6-phenyl-5-sulfanylhexanoyl]-L-alanine
Homo sapiens
pH and temperature not specified in the publication
0.000012
N-[2-(biphenyl-4-ylmethyl)-6-methyl-4-oxo-5-sulfanyloctanoyl]-L-alanine
Homo sapiens
pH and temperature not specified in the publication
0.00001
N-[2-benzyl-6-(4-bromophenyl)-4-oxo-5-sulfanylhexanoyl]-L-leucine
Homo sapiens
pH and temperature not specified in the publication
0.00001 - 0.021
phosphoramidon
0.0000005
tert-butyl 2-([1-[(5-benzyl-1,3,4-thiadiazol-2-yl)carbamoyl]cyclopentyl]methyl)-4-methoxybutanoate
Canis lupus familiaris
-
-
0.00001 - 0.077
thiorphan
0.0000003
(2R)-2-[[1-([(1S)-1-carboxy-2-[5-(4-chlorophenyl)-1,3-oxazol-2-yl]ethyl]carbamoyl)cyclopentyl]methyl]-5-oxopentanoic acid
Homo sapiens
-
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
Homo sapiens
-
pH and temperature not specified in the publication
0.00001
phosphoramidon
Homo sapiens
wild-type enzyme, pH and temperature not specified in the publication
0.000075
phosphoramidon
Homo sapiens
enzyme mutant G714K, pH and temperature not specified in the publication
0.0044
phosphoramidon
Homo sapiens
enzyme mutant G399V, pH and temperature not specified in the publication
0.021
phosphoramidon
Homo sapiens
enzyme mutant G399V/G714K, pH and temperature not specified in the publication
0.00001
thiorphan
Homo sapiens
below, wild-type enzyme, pH and temperature not specified in the publication
0.077
thiorphan
Homo sapiens
enzyme mutant G399V/G714K, pH and temperature not specified in the publication
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-
adipocyte membrane
brenda
-
-
brenda
-
-
brenda
-
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
brenda
-
mature
brenda
-
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
brenda
-
-
brenda
-
-
brenda
-
a large fraction of the enzyme is localized on intrinsic striatal neurons
brenda
-
-
brenda
-
from articular cartilage
brenda
-
-
brenda
-
brenda
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
brenda
-
-
brenda
-
-
brenda
-
-
brenda
-
-
brenda
-
-
brenda
-
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
brenda
-
-
brenda
-
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
brenda
-
high activity
brenda
-
-
brenda
-
-
brenda
-
-
brenda
-
brenda
-
-
brenda
-
-
brenda
osteoblastic cell line PyMS
brenda
-
neutral endopeptidase 24.11/CD10 is expressed in tumor cells as well as stromal tissues
brenda
-
-
brenda
-
-
brenda
-
-
brenda
-
brenda
-
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
brenda
-
-
brenda
-
-
brenda
-
high activity in glandular epithelium, weak activity in stroma
brenda
-
-
brenda
-
-
brenda
-
-
brenda
-
-
brenda
-
present in many, but not all Schwann cell membranes
brenda
-
-
brenda
-
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
brenda
-
-
brenda
-
polyclonal
brenda
-
capsule, subcapsular zone, Hassall's corpuscles
brenda
-
brenda
-
-
brenda
-
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
brenda
-
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
brenda
-
-
brenda
-
brenda
-
-
brenda
-
dura and pia mater
brenda
-
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
brenda
the enzyme level is reduced in the brains of patients with Alzheimer's disease
brenda
-
-
brenda
-
brenda
-
-
brenda
-
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
brenda
-
-
brenda
-
in globus pallidus and substantia nigra much of the enzyme is associated with presynaptic nerve terminals originating from efferent striatal neurons
brenda
-
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
brenda
-
enzyme in sustantia nigra and globus pallidus is localized on nerve terminals originating from neurones in the caudate putamen
brenda
-
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
brenda
-
temporal cortex of amyloid beta(25-35)-infused and healthy rats
brenda
-
ethanol induces a transitory increase in NEP activities in the frontal cortex and ventral tegmental area, and in the nucleus accumbens
brenda
six-week intermittent hypoxia increases NEP expression and activity, selectively in temporal cortex, but not in the hippocampus and frontal cortex. The increase in NEP activity and expression is reverted followed by two weeks recovery in normoxia
brenda
-
six-week intermittent hypoxia increases NEP expression and activity, selectively in temporal cortex, but not in the hippocampus and frontal cortex. The increase in NEP activity and expression is reverted followed by two weeks recovery in normoxia
-
brenda
-
-
brenda
-
striatum
brenda
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pial membranes associated with brain and spinal cord
brenda
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medulla, paracortex, cortex
brenda
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corpus striatum and globus pallidus
brenda
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synaptic membranes
brenda
-
-
brenda
-
brenda
-
-
brenda
-
-
brenda
-
-
brenda
-
low level of neprilysin. Amyloid-beta deposition appears in the cerebral cortex and the hippocampus
brenda
-
low level of neprilysin. Amyloid-beta deposition appears in the cerebral cortex and the hippocampus
brenda
-
brenda
recombinant rhNEP
brenda
-
distribution of neprilysin is high in the striatum, globus pallidus, and substantia nigra, but very low in the cerebral cortex
brenda
-
distribution of neprilysin is high in the striatum, globus pallidus, and substantia nigra, but very low in the cerebral cortex
brenda
-
-
brenda
-
brenda
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cerebral endothelial cell culture
brenda
-
-
brenda
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-
brenda
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-
brenda
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-
brenda
-
brenda
-
brenda
-
embryonic
brenda
-
-
brenda
-
-
brenda
-
brenda
-
distribution of neprilysin is high in the striatum, globus pallidus, and substantia nigra, but very low in the cerebral cortex
brenda
-
distribution of neprilysin is high in the striatum, globus pallidus, and substantia nigra, but very low in the cerebral cortex
brenda
hair follicles are isolated from occipital scalp specimens, enzyme is localized in extracellular matrix, dermal papilla, and follicular epithelium, and during all stages of the hair cycle
brenda
-
brenda
extracellular matrix, dermal papilla, and follicular epithelium
brenda
-
brenda
-
brenda
-
brenda
-
brenda
-
-
brenda
-
amyloid-beta deposition appears in the cerebral cortex and the hippocampus
brenda
-
amyloid-beta deposition appears in the cerebral cortex and the hippocampus
brenda
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-
brenda
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neurons
brenda
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-
brenda
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-
brenda
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anterior
brenda
-
-
brenda
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-
brenda
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-
brenda
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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
brenda
-
-
brenda
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-
brenda
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glomeruli, tubules
brenda
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-
brenda
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-
brenda
-
neprilysin specific activity varies across mouse strains, with the highest activities in kidney and brain of SW mice
brenda
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-
brenda
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renal brush border
brenda
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-
brenda
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cortex
brenda
-
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
brenda
-
-
brenda
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cortex
brenda
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microvillar membrane
brenda
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renal brush border
brenda
-
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
brenda
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-
brenda
-
brenda
-
-
brenda
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-
brenda
-
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
brenda
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-
brenda
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body wall musculature
brenda
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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
brenda
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in neuroblastoma SH-SY5Y cells neprilysin expression is up-regulated estrogen
brenda
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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
brenda
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expression of nep-1 is limited to pharyngeal cells and a single head neuron
brenda
-
brenda
CA1 neuron, NEP is almost exclusively expressed in neurons. Presynaptic terminals and intracellular locations are likely the main sites of NEP-mediated amyloid-beta degradation
brenda
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hippocampal
brenda
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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
brenda
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androgens positively regulate neural expression of neprilysin in adult male rats
brenda
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chromatin immunoprecipitation analysis demonstrates amyloid precursor protein binding to tht NEP promoter in primary neurons
brenda
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-
brenda
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-
brenda
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-
brenda
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-
brenda
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brenda
differentiated
brenda
the enzyme activity in the skin is elevated at early anagen, and decreased during catagen to telogen of the hair cycle
brenda
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brenda
the enzyme activity in the skin is elevated at early anagen, and decreased during catagen to telogen of the hair cycle
brenda
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brenda
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-
brenda
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-
brenda
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pial membranes associated with brain and spinal cord
brenda
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distribution of neprilysin is high in the striatum, globus pallidus, and substantia nigra, but very low in the cerebral cortex
brenda
-
distribution of neprilysin is high in the striatum, globus pallidus, and substantia nigra, but very low in the cerebral cortex
brenda
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-
brenda
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-
brenda
additional information
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the enzyme is expressed all along the differentiation pathway in B and T cell lineage
brenda
additional information
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no activity of CD10/neutral endopeptidase is detected in cultured, non-stimulated keratinocytes from healthy skin
brenda
additional information
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in cerebrocortical blood vessels and in pyramidal neurons
brenda
additional information
membrane-bound NEP from cells overexpressing the murine peptidase
brenda
additional information
-
membrane-bound NEP from cells overexpressing the murine peptidase
brenda
additional information
expression and activity of NEP in cognitive-related brain structures of rats submitted to chronic intermittent hypoxia (CIH)
brenda
additional information
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expression and activity of NEP in cognitive-related brain structures of rats submitted to chronic intermittent hypoxia (CIH)
-
brenda
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evolution
neprilysin is a plasma membrane glycoprotein of the neutral zinc metalloendopeptidase family
evolution
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neprilysin is a zinc metalloendopeptidase belonging to the M13 family
evolution
neprilysin is a zinc metalloendopeptidase belonging to the M13 family
evolution
neprilysin is a zinc metalloendopeptidase belonging to the M13 family
evolution
the enzyme harbors an ectodomain, which contains the catalytic site and belongs to the M13 family of peptidases/proteases
evolution
the enzyme is a member of the M13 subgroup of the zinc-dependent endopeptidase family
evolution
neprilysin is a zinc dependent type II integral membrane peptidase belonging to the M13 family
evolution
sequence comparisons of NEP and NEP-2 (EC 3.4.24._)
evolution
sequence comparisons of NEP and NEP-2
malfunction
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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
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following overexpression of neprilysin using an adenovirus encoding neprilysin islet amyloid deposition and beta-cell apoptosis both decrease by 79%
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
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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
malfunction
application of inhibitors to NEP in mouse brain produced dramatic elevations of endogenous amyloid beta peptide resulting in plaque deposition. But enzyme knockout mice show only a moderate increase in amyloid beta levels that are far from the levels needed to induce plaque deposition. This modest increase in amyloid beta peptide raises the possibility of alternative amyloid beta degrading-enzymes that are likewise sensitive to NEP-inhibitors
malfunction
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application of inhibitors to NEP in rat brain produced dramatic elevations of endogenous amyloid beta peptide resulting in plaque deposition
malfunction
enzyme inhibition augmentes the maximum hemodynamic effects of pulmonary vasodilation by pulmonary vasodilative vasoactive intestinal peptide, VIP, aerosol, and also leads to a significant prolongation of these effects
malfunction
inhibitor N-phenethylphosphonyl-L-leucyl-L-tryptophane-treated mouse skin elastic fibers surrounding early anagen hair cycle phase hair bulbs seem to accumulate more than in vehicle-treated mouse skin
malfunction
treatment of cells with TPI2155-14 and TPI2155-17, specific inhibitors for ADAM-17 protease, EC 3.4.24.86, results in a significant decrease in neprilysin activity in media, implicating a possible role for ADAM-17 in neprilysin release
malfunction
a lack of 465 NEP accelerates hippocampal neuron loss in relatively young transgenic mice expressing amyloid-beta4-42
malfunction
inhibitors of NEP with a lesser degree of specificity can treat hypertension with an increased risk of cerebral deposition of amyloid-beta
malfunction
NEP inhibition leads to an increased level of vasoactive peptides such as atrial natriuretic peptide, brain natriuretic peptide, bradykinin, adrenomedullin, and endothelin-1. The combination of NEP and angiotensin receptor inhibition is superior to either agent alone and leads to vasodilation and reduction of extracellular fluid via sodium excretion
metabolism
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neprilysin-2 (NEP2), a NEP-like endopeptidase, cooperates with neprilysin (NEP) to control amyloid-beta peptide levels in the brain
metabolism
neprilysin-2 (NEP2), a NEP-like endopeptidase, cooperates with neprilysin (NEP) to control amyloid-beta peptide levels in the brain
metabolism
neprilysin-2 (NEP2), a NEP-like endopeptidase, cooperates with neprilysin (NEP) to control amyloid-beta peptide levels in the brain
metabolism
the non-membrane bound form of neprilysin with catalytic activity has the potential to cleave substrates throughout the blood circulation with systemic effects. A likely role of exosomes and protease ADAM-17 in release of the enzyme, overview
metabolism
in the peripheral system, neutral endopeptidase neprilysin (NEP) regulates hypertension and heart related diseases, while its closest homologue, neprilysin-2 (NEP2, EC 3.4.24._), in the central nervous system controls Alzheimer's protein (amyloid-beta) deposition, and prevents its occurrence
metabolism
in the peripheral system, neutral endopeptidase neprilysin (NEP) regulates hypertension and heart related diseases, while its closest homologue, neprilysin-2 (NEP2), in the central nervous system controls Alzheimer's protein (amyloid-beta) deposition, and prevents its occurrence
physiological function
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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
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
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
-
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
-
molecular interactions between arsenic microcrystals and membrane-bound CD10 to be implicated in arsenic-induced carcinogenesis
physiological function
-
neprilysin decreases islet amyloid deposition by inhibiting human islet amyloid polypeptide fibril formation, rather than degrading human islet amyloid polypeptide
physiological function
amyloid beta-induced death of hippocampal neuron of APP/PS1 mice is inhibited by human recombinant soluble enzyme, overview
physiological function
neprilysin is a neutral endopeptidase, is one of the major amyloid beta-degrading enzymes in the brain
physiological function
the enzyme degrades a number of physiological peptides that are involved in processes such as blood pressure regulation and nociception
physiological function
the enzyme inhibits the pulmonary vasodilation by pulmonary vasodilative vasoactive intestinal peptide, VIP, in lungs of subjects with pathophysiology of pulmonary hypertension (due to a deficiency in VIP) by rapid inactivation of VIP
physiological function
the role of neprilysin in regulating the hair cycle, a cyclic process of growing, regressing and resting phases, i.e. anagen, catagen, and telogen, respectively. The enzyme degrades elastin, which is associated with skin elasticity
physiological function
the role of neprilysin in regulating the hair cycle, a cyclic process of growing, regressing and resting phases, i.e. anagen, catagen, and telogen, respectively. The enzyme degrades elastin, which is associated with skin elasticity
physiological function
the role of neprilysin in regulating the hair cycle, a cyclic process of growing, regressing and resting phases, i.e. anagen, catagen, and telogen, respectively. The enzyme degrades elastin, which is associated with skin elasticity
physiological function
N-terminal truncated Abeta4-42 is a substrate for neprilysin degradation in vitro and in vivo
physiological function
neprilysin (NEP) is responsible for degrading several substrates related to cognition
physiological function
neprilysin degrades a variety of vasoactive peptides such as atrial natriuretic peptide, brain natriuretic peptide, bradykinin, adrenomedullin, and endothelin-1
physiological function
neprilysin inhibits coagulation through proteolytic inactivation of fibrinogen. The enzyme may have a role in regulating fibrin formation. Wild-type HSA-NEP and mutant HSA-NEPv impair coagulation, increasing prothrombin time (PT) and activated partial thromboplastin time (APTT) in plasma samples and abolishing fibrin formation from fibrinogen. This effect is mediated through cleavage of the N-termini of the Aalpha- and Bbeta-chains of fibrinogen thereby significantly impairing initiation of fibrin formation by thrombin
physiological function
neprilysin is a transmembrane M13 zinc metalloprotease responsible for the degradation of several biologically active peptides including insulin, enkephalin, substance P, bradykinin, endothelin-1, neurotensin and amyloid-beta
physiological function
neutral endopeptidase neprilysin (NEP) regulates hypertension and heart related diseases
physiological function
the metalloprotease neprilysin degrades and inactivates apelin peptides. The apelinergic system is a mammalian peptide hormone network with key physiological roles. Apelin isoforms and analogues are believed to be promising therapeutics for cardiovascular disease. Involvement of NEP in the apelinergic system. In vitro NEP proteolysis generates fragments that lack the ability to bind to the apelin receptor, NEP protease fully inactivates apelin
physiological function
-
neprilysin (NEP) is responsible for degrading several substrates related to cognition
-
additional information
protease activities of the mature form of the enzyme do not differ between lipid rafts and nonlipid rafts. Cholesterol and other lipids regulate the localization of mature enzyme to lipid rafts, where the substrate amyloid beta peptide accumulates but does not modulate the protease activity of the enzyme
additional information
protein-ligand docking calculations predict S2' subsite residues Arg102 and Arg110 of the enzyme to participate in specific interactions with amyloid beta peptide and are a target for modification of the enzyme for higher specificity against amyloid beta peptide
additional information
the enzyme is composed of an ectodomain, which contains the catalytic site, a transmembrane domain and a short intracellular domain. The structure of the ectodomain is composed of two largely alpha-helical domains that are arranged to form a central spherical water-filled core that contains the active site of the enzyme
additional information
molecular dynamics (MD) simulations of NEP and modelling, overview. For substrate and inhibitor binding, Arg664 and Zn697 are identified as the most conserved residues
additional information
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molecular dynamics (MD) simulations of NEP and modelling, overview. For substrate and inhibitor binding, Arg664 and Zn697 are identified as the most conserved residues
additional information
selectivity of the compound LBQ657 for NEP relative to the homologous peptidases, endothelin converting enzyme (ECE-1) and neprilysin 2 (NEP2)
additional information
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selectivity of the compound LBQ657 for NEP relative to the homologous peptidases, endothelin converting enzyme (ECE-1) and neprilysin 2 (NEP2)
additional information
the enzyme contains the HEXXH motif. The zinc ion is coordinated by conserved residues H583 and H587 and additional coordination is provided by E646. The third conserved residue, E584, is involved in the catalytic mechanism and adopts a position above the zinc ion completing coordination sphere. Active site flexibility and modelling, overview. Enzyme crystal structure comparisons
additional information
-
the enzyme contains the HEXXH motif. The zinc ion is coordinated by conserved residues H583 and H587 and additional coordination is provided by E646. The third conserved residue, E584, is involved in the catalytic mechanism and adopts a position above the zinc ion completing coordination sphere. Active site flexibility and modelling, overview. Enzyme crystal structure comparisons
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E12A
site-directed mutagenesis, the mutant cannot be stimulated by myotoxin II-derived peptides from Bothrops acer
E403C
site-directed mutagenesis, homodimerization mutant, reduced localization in lipid rafts
E4A
site-directed mutagenesis, the mutant cannot be stimulated by myotoxin II-derived peptides from Bothrops acer
F3A
site-directed mutagenesis, the mutant cannot be stimulated by myotoxin II-derived peptides from Bothrops acer
F563I
site-directed mutagenesis, active site mutant which displays an increase in preference towards cleaving leucine5-enkephalin relative to insulin B chain, reduced activity with glutaryl-Ala-Ala-Phe-MNA compared to the wild-type enzyme
F563L
site-directed mutagenesis, active site mutant which exhibits different cleavage site preferences with insulin B chain and amyloid beta1-40 as substrates compared to the wild-type enzyme, similar activity with glutaryl-Ala-Ala-Phe-MNA as the wild-type enzyme
F563M
site-directed mutagenesis, active site mutant which exhibits reduced activity with glutaryl-Ala-Ala-Phe-MNA compared to the wild-type enzyme
F563V
site-directed mutagenesis, active site mutant which exhibits reduced activity with glutaryl-Ala-Ala-Phe-MNA compared to the wild-type enzyme
G399V
site-directed mutagenesis, the mutant shows increased catalytic efficiency on Ab1-40 with 6fold increased catalytic efficiency compared to the wild-type enzyme. The G399V mutation also significantly reduces the catalytic efficiency on angiotensin, bradykinin and neurotensin compared to the wild-type enzyme
G714K
site-directed mutagenesis, the mutant shows increased catalytic efficiency on Ab1-40 with 6fold increased catalytic efficiency compared to the wild-type enzyme
K15A
site-directed mutagenesis, the mutant cannot be stimulated by myotoxin II-derived peptides from Bothrops acer
K19A
site-directed mutagenesis, the mutant cannot be stimulated by myotoxin II-derived peptides from Bothrops acer
L10A
site-directed mutagenesis, the mutant cannot be stimulated by myotoxin II-derived peptides from Bothrops acer
L2A
site-directed mutagenesis, the mutant cannot be stimulated by myotoxin II-derived peptides from Bothrops acer
S20A
site-directed mutagenesis, the mutant cannot be stimulated by myotoxin II-derived peptides from Bothrops acer
S546A
site-directed mutagenesis, active site mutant with highly reduced activity compared to the wild-type enzyme
S546E
site-directed mutagenesis, active site mutant, that is less discriminating than wild-type neprilysin and exhibits different cleavage site preferences with insulin B chain and amyloid beta1-40 as substrates, reduced activity with glutaryl-Ala-Ala-Phe-MNA compared to the wild-type enzyme
S546T
site-directed mutagenesis, active site mutant with highly reduced activity compared to the wild-type enzyme
T13A
site-directed mutagenesis, the mutant cannot be stimulated by myotoxin II-derived peptides from Bothrops acer
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
H637F
-
no effect on activity
V580L
-
change in substrate specificity
E584V
site-directed mutagenesis, catalytically inactive mutant, negative control
E584V
site-directed mutagenesis, inactive mutant, has no effects on prothrombin time (PT) and activated partial thromboplastin time (APTT) in rats and monkeys
G399V/G714K
site-directed mutagenesis, the enzyme variant displays an approximately 20fold improved activity on amyloid beta 1-40 and up to a 3200fold reduction in activity on other peptides, and the mutant enzyme produces a markedly altered series of amyloid beta cleavage products compared to the wild-type enzyme
G399V/G714K
site-directed mutagenesis, the engineered NEP, HSA-NEPv G399V/G714K, has a potential as therapeutic for Alzheimer disease but in pre-clinical safety testing, this variant increases prothrombin time (PT) and activated partial thromboplastin time (APTT) measured in cynomolgus monkeys and rats dosed with a human serum albumin fusion with an engineered variant of NEP as well as in control plasma spiked with wild-type or mutant enzyme. Wild-type HSA-NEP and mutant HSA-NEPv impair coagulation, increasing PT and APTT in plasma samples and abolishing fibrin formation from fibrinogen. This effect is mediated through cleavage of the N-termini of the Aalpha- and Bbeta-chains of fibrinogen thereby significantly impairing initiation of fibrin formation by thrombin. The effects on PT and APTT are broadly similar in male and female rats although the effect on APTT is less clear cut in females
H583F
-
enzymatic activity and Zn-directed inhibitor binding is abolished
H587F
-
enzymatic activity and Zn-directed inhibitor binding is abolished
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
-
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
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
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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
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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%
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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
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generation of a soluble version of the ectodomain of neprilysin with improved activity and specificity towards amyloid beta peptide as a potential therapeutic for Alzheimer's disease
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it is possible to alter the cleavage site specificity of neprilysin opening the way for the development of substrate specific or substrate exclusive forms of the enzyme with enhanced therapeutic potential
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viral expression of NEP in primary neurons leads to effective clearance of amylod-beta in vitro
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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
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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
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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
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