3.4.24.11 (2(R,S)-2-sulfanyl-2-benzyl)acetyl-Ala-Pro - 72565 3.4.24.11 (2(R,S)-2-sulfanyl-2-benzyl)acetyl-Leu-Tyr - 72566 3.4.24.11 (2(R,S)-2-sulfanyl-2-benzyl)acetyl-Phe-Ala - 72567 3.4.24.11 (2(R,S)-2-sulfanyl-2-benzyl)acetyl-Phe-Tyr - 72568 3.4.24.11 (2(R,S)-2-sulfanyl-2-isopropyl)acetyl-Ile-Tyr - 72569 3.4.24.11 (2R)-2-(biphenyl-4-ylmethyl)-6-[4-[cyclohexyl(sulfanyl)methyl]phenyl]-4-oxo-5-sulfanylhexanoic acid - 237647 3.4.24.11 (2R)-2-([1-[(5-ethyl-1,3,4-thiadiazol-2-yl)carbamoyl]cyclopentyl]methyl)pentanoic acid - 67733 3.4.24.11 (2R)-2-[(1-[[(1S)-1-carboxy-2-(3-phenyl-1,2,4-oxadiazol-5-yl)ethyl]carbamoyl]cyclopentyl)methyl]-5-oxopentanoic acid - 86800 3.4.24.11 (2R)-2-[(1-[[(1S)-1-carboxy-2-(4-ethyl-1,3-oxazol-2-yl)ethyl]carbamoyl]cyclopentyl)methyl]pentanoic acid - 86793 3.4.24.11 (2R)-2-[(1-[[(1S)-1-carboxy-2-(4-phenyl-1,3-oxazol-2-yl)ethyl]carbamoyl]cyclopentyl)methyl]-5-oxopentanoic acid - 86797 3.4.24.11 (2R)-2-[(1-[[(1S)-1-carboxy-2-(4-phenyl-1,3-oxazol-2-yl)ethyl]carbamoyl]cyclopentyl)methyl]pentanoic acid - 86795 3.4.24.11 (2R)-2-[(1-[[(1S)-1-carboxy-2-(5-phenyl-1,3,4-oxadiazol-2-yl)ethyl]carbamoyl]cyclopentyl)methyl]-5-oxopentanoic acid - 86799 3.4.24.11 (2R)-2-[(1-[[(1S)-1-carboxy-2-(5-phenyl-1,3-oxazol-2-yl)ethyl]carbamoyl]cyclopentyl)methyl]-5-oxopentanoic acid - 86798 3.4.24.11 (2R)-2-[(1-[[(1S)-1-carboxy-2-(5-phenyl-1,3-oxazol-2-yl)ethyl]carbamoyl]cyclopentyl)methyl]pentanoic acid - 86796 3.4.24.11 (2R)-2-[[1-([(1S)-1-carboxy-2-[4-(2-methylpropyl)-1,3-oxazol-2-yl]ethyl]carbamoyl)cyclopentyl]methyl]pentanoic acid - 86794 3.4.24.11 (2R)-2-[[1-([(1S)-1-carboxy-2-[5-(4-chlorophenyl)-1,3-oxazol-2-yl]ethyl]carbamoyl)cyclopentyl]methyl]-5-oxopentanoic acid - 41902 3.4.24.11 (2R)-6-[4-[cyclohexyl(sulfanyl)methyl]phenyl]-4-oxo-5-sulfanyl-2-[4-(thiophen-3-yl)benzyl]hexanoic acid - 237703 3.4.24.11 (2S)-2-(biphenyl-4-ylmethyl)-6-[4-[cyclohexyl(sulfanyl)methyl]phenyl]-4-oxo-5-sulfanylhexanoic acid - 237758 3.4.24.11 (2S)-2-[(1-[[2-(hydroxymethyl)-2,3-dihydro-1H-inden-2-yl]carbamoyl]cyclopentyl)methyl]-4-methoxybutanoic acid - 67737 3.4.24.11 (2S)-2-[(1-[[3-(4-chlorophenyl)propyl]carbamoyl]cyclopentyl)methyl]-4-methoxybutanoic acid - 67738 3.4.24.11 (2S)-2-[(1-[[3-(4-fluorophenyl)propyl]carbamoyl]cyclopentyl)methyl]-4-methoxybutanoic acid - 67739 3.4.24.11 (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) - 86792 3.4.24.11 (2S)-4-methoxy-2-([1-[(1-methyl-2-phenylethyl)carbamoyl]cyclopentyl]methyl)butanoic acid - 67745 3.4.24.11 (2S)-4-methoxy-2-[(1-[[(1R,2S)-2-(4-methoxyphenyl)cyclopropyl]carbamoyl]cyclopentyl)methyl]butanoic acid - 67746 3.4.24.11 (2S)-6-[4-[cyclohexyl(sulfanyl)methyl]phenyl]-4-oxo-5-sulfanyl-2-[4-(thiophen-3-yl)benzyl]hexanoic acid - 237764 3.4.24.11 (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 160191 3.4.24.11 1,10-phenanthroline - 62 3.4.24.11 2,3-Dimercaptopropan-1-ol weak 15468 3.4.24.11 2-(1-heptylcarbamoyl-cyclopentylmethyl)-4-methoxy-butyric acid tert-butyl ester - 67854 3.4.24.11 2-(4-bromobenzyl)-4-oxo-5-sulfanyl-6-[4-(2-sulfanylpropan-2-yl)phenyl]hexanoic acid - 238136 3.4.24.11 2-(4-bromobenzyl)-4-oxo-5-sulfanyl-6-[4-(3-sulfanylpentan-3-yl)phenyl]hexanoic acid - 238137 3.4.24.11 2-(4-bromobenzyl)-4-oxo-6-phenyl-5-sulfanylhexanoic acid - 238138 3.4.24.11 2-(4-bromobenzyl)-4-oxo-6-[4-[piperidin-4-yl(sulfanyl)methyl]phenyl]-5-sulfanylhexanoic acid - 238139 3.4.24.11 2-(4-bromobenzyl)-6-(4-bromophenyl)-4-oxo-5-sulfanylhexanoic acid - 238140 3.4.24.11 2-(4-bromobenzyl)-6-[4-(butan-2-yl)phenyl]-1-(morpholin-4-yl)-5-sulfanylhexane-1,4-dione - 238141 3.4.24.11 2-(4-bromobenzyl)-6-[4-(butan-2-yl)phenyl]-4-oxo-5-sulfanylhexanoic acid - 238142 3.4.24.11 2-(4-bromobenzyl)-6-[4-[2,3-dihydro-1H-inden-2-yl(sulfanyl)methyl]phenyl]-4-oxo-5-sulfanylhexanoic acid - 238143 3.4.24.11 2-(4-bromobenzyl)-6-[4-[cyclohexyl(sulfanyl)methyl]phenyl]-4-oxo-5-sulfanylhexanoic acid - 238144 3.4.24.11 2-(4-bromobenzyl)-6-[4-[cyclopentyl(sulfanyl)methyl]phenyl]-4-oxo-5-sulfanylhexanoic acid - 238145 3.4.24.11 2-(biphenyl-4-ylmethyl)-4-oxo-6-[4-[piperidin-4-yl(sulfanyl)methyl]phenyl]-5-sulfanylhexanoic acid - 238166 3.4.24.11 2-(biphenyl-4-ylmethyl)-6-[4-[2,3-dihydro-1H-inden-2-yl(sulfanyl)methyl]phenyl]-4-oxo-5-sulfanylhexanoic acid - 238167 3.4.24.11 2-(biphenyl-4-ylmethyl)-6-[4-[cyclohexyl(sulfanyl)methyl]phenyl]-4-oxo-5-sulfanylhexanoic acid - 238168 3.4.24.11 2-(biphenyl-4-ylmethyl)-6-[4-[cyclopentyl(sulfanyl)methyl]phenyl]-4-oxo-5-sulfanylhexanoic acid - 238169 3.4.24.11 2-([1-[(1,3-benzodioxol-5-ylmethyl)carbamoyl]cyclopentyl]methyl)pentanoic acid IC50: 1500 nM 59818 3.4.24.11 2-([1-[(1-benzyl-2-hydroxyethyl)carbamoyl]cyclopentyl]methyl)pentanoic acid IC50: 384 nM 59825 3.4.24.11 2-([1-[(1-benzyl-6-oxo-1,6-dihydropyridin-3-yl)carbamoyl]cyclopentyl]methyl)pentanoic acid IC50: 313 nM 59832 3.4.24.11 2-([1-[(1-ethyl-1H-1,2,3-triazol-4-yl)carbamoyl]cyclopentyl]methyl)pentanoic acid IC50: 82 nM 59826 3.4.24.11 2-([1-[(3-ethylpyridin-2-yl)carbamoyl]cyclopentyl]methyl)pentanoic acid IC50: 1710 nM 59829 3.4.24.11 2-([1-[(4-benzylpyridin-2-yl)carbamoyl]cyclopentyl]methyl)pentanoic acid IC50: 96 nM 59831 3.4.24.11 2-([1-[(4-butylpyridin-2-yl)carbamoyl]cyclopentyl]methyl)pentanoic acid IC50: 184 nM 59830 3.4.24.11 2-([1-[(4-carbamoylcyclohexyl)carbamoyl]cyclopentyl]methyl)pentanoic acid IC50: 150 nM 59845 3.4.24.11 2-([1-[(5-benzyl-1,3,4-thiadiazol-2-yl)carbamoyl]cyclopentyl]methyl)pentanoic acid IC50: 30 nM 59836 3.4.24.11 2-([1-[(5-ethyl-1,3,4-thiadiazol-2-yl)carbamoyl]cyclopentyl]methyl)-4-phenylbutanoic acid IC50: 46 nM 59848 3.4.24.11 2-([1-[(5-ethyl-1,3,4-thiadiazol-2-yl)carbamoyl]cyclopentyl]methyl)-5-methylhexanoic acid IC50: 120 nM 59849 3.4.24.11 2-([1-[(5-ethyl-1,3,4-thiadiazol-2-yl)carbamoyl]cyclopentyl]methyl)hexanoic acid IC50: 84 nM 59846 3.4.24.11 2-([1-[(5-ethyl-1,3,4-thiadiazol-2-yl)carbamoyl]cyclopentyl]methyl)pentanoic acid IC50: 60 nM 59824 3.4.24.11 2-([1-[(5-methyl-1,3,4-thiadiazol-2-yl)carbamoyl]cyclopentyl]methyl)pentanoic acid IC50: 176 nM 59819 3.4.24.11 2-([1-[(5-phenyl-1,3,4-thiadiazol-2-yl)carbamoyl]cyclopentyl]methyl)pentanoic acid IC50: 283 nM 59834 3.4.24.11 2-([1-[(6-methoxypyridazin-3-yl)carbamoyl]cyclopentyl]methyl)pentanoic acid IC50: 374 nM 59827 3.4.24.11 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 59850 3.4.24.11 2-benzyl-4-oxo-6-phenyl-5-sulfanylhexanoic acid - 238176 3.4.24.11 2-benzyl-6-(4-bromophenyl)-4-oxo-5-sulfanylhexanoic acid - 238177 3.4.24.11 2-mercaptoethanol - 63 3.4.24.11 2-methoxymethyl-3-[1-(trans-2-phenyl-cyclopropylcarbamoyl)-cyclopentyl]-propionic acid tert-butyl ester - 69199 3.4.24.11 2-[(1-[[(1R)-1-phenylethyl]carbamoyl]cyclopentyl)methyl]pentanoic acid IC50: 530 nM 59821 3.4.24.11 2-[(1-[[(1R)-3-(dimethylcarbamoyl)cyclohexyl]carbamoyl]cyclopentyl)methyl]pentanoic acid IC50: 297 nM 59842 3.4.24.11 2-[(1-[[(1R,2R)-2-benzylcyclohexyl]carbamoyl]cyclopentyl)methyl]pentanoic acid IC50: 195 nM 59839 3.4.24.11 2-[(1-[[(1R,2S)-2-propylcyclohexyl]carbamoyl]cyclopentyl)methyl]pentanoic acid IC50: 890 nM 59840 3.4.24.11 2-[(1-[[(3R)-1-benzylpyrrolidin-3-yl]carbamoyl]cyclopentyl)methyl]pentanoic acid IC50: 1060 nM 59843 3.4.24.11 2-[(1-[[(3R)-1-carbamoylpyrrolidin-3-yl]carbamoyl]cyclopentyl)methyl]pentanoic acid IC50: 213 nM 59844 3.4.24.11 2-[(1-[[(5-methyl-1,3,4-thiadiazol-2-yl)methyl]carbamoyl]cyclopentyl)methyl]pentanoic acid IC50: 700 nM 59838 3.4.24.11 2-[(1-[[1-(hydroxymethyl)cyclopentyl]carbamoyl]cyclopentyl)methyl]pentanoic acid IC50: 1710 nM 59820 3.4.24.11 2-[(1-[[2-(hydroxymethyl)-2,3-dihydro-1H-inden-2-yl]carbamoyl]cyclopentyl)methyl]pentanoic acid IC50: 96 nM 59822 3.4.24.11 2-[(1-[[4-(dimethylcarbamoyl)cyclohexyl]carbamoyl]cyclopentyl)methyl]pentanoic acid IC50: 370 nM 59841 3.4.24.11 2-[(1-[[5-(2-methylpropyl)-1,3,4-thiadiazol-2-yl]carbamoyl]cyclopentyl)methyl]pentanoic acid IC50: 124 nM 59835 3.4.24.11 2-[(1-[[5-(cyclopropylmethyl)-1,3,4-thiadiazol-2-yl]carbamoyl]cyclopentyl)methyl]pentanoic acid IC50: 38 nM 59837 3.4.24.11 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 99802 3.4.24.11 2-[(3-iodohydroxy)phenylmethyl]-4-N-[3-hydroxyamino-3-oxo-1-phenylmethylpropyl]-amino-4-oxobutanoic acid i.e. RB104, highly selective and potent inhibitor 99803 3.4.24.11 2-[1-(2-hydroxymethyl-indan-2-ylcarbamoyl)-cyclopentylmethyl]-4-methoxy-butyric acid tert-butyl ester - 67873 3.4.24.11 2-[1-(4-butyl-pyridin-2-ylcarbamoyl)-cyclopentylmethyl]-4-methoxybutyric acid benzyl ester - 67874 3.4.24.11 2-[1-(5-ethyl-[1,3,4]thiadiazol-2-ylcarbamoyl)-cyclopentylmethyl]-pentanoic acid - 69480 3.4.24.11 2-[1-[2-(trans-4-chlorophenyl)-cyclopropylcarbamoyl]-cyclopentylmethyl]-4-methoxy-butyric acid tert-butyl ester - 67875 3.4.24.11 2-[1-[3-(4-chloro-phenyl)-propylcarbamoyl]-cyclopentylmethyl]-4-methoxy-butyric acid tert-butyl ester - 67876 3.4.24.11 2-[1-[3-(4-fluoro-phenyl)-propylcarbamoyl]-cyclopentylmethyl]-4-methoxy-butyric acid tert-butyl ester - 67877 3.4.24.11 2-[[1-(1,3,4-thiadiazol-2-ylcarbamoyl)cyclopentyl]methyl]pentanoic acid IC50: 377 nM 59833 3.4.24.11 2-[[1-(2,3-dihydro-1H-inden-2-ylcarbamoyl)cyclopentyl]methyl]pentanoic acid IC50: 313 nM 59823 3.4.24.11 2-[[1-(5-benzyl-1,3,4-oxadiazol-2-yl)cyclopentyl]methyl]pentanoic acid IC50: 3100 nM 59851 3.4.24.11 2-[[1-(pyridin-2-ylcarbamoyl)cyclopentyl]methyl]pentanoic acid IC50: 1500 nM 59828 3.4.24.11 3-[1-[(5-ethyl-1,3,4-thiadiazol-2-yl)carbamoyl]cyclopentyl]propanoic acid IC50: 237 nM 59847 3.4.24.11 3-[1-[2-(trans-4-chlorophenyl)-cyclopropylcarbamoyl]-cyclopentyl]-2-methoxymethyl-propionic acid tert-butyl ester - 67943 3.4.24.11 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 37847 3.4.24.11 4-methoxy-2-(1-phenethylcarbamoyl-cyclopentylmethyl)-butyric acid benzyl ester - 67981 3.4.24.11 4-methoxy-2-[1-(3-phenyl-propylcarbamoyl)-cyclopentylmethyl]-butyric acid tert-butyl ester - 67982 3.4.24.11 4-methoxy-2-[1-(trans-2-pentyl-cyclopropylcarbamoyl)-cyclopentylmethyl]-butyric acid tert-butyl ester - 67983 3.4.24.11 4-methoxy-2-[1-(trans-2-phenyl-cyclopropylcarbamoyl)-cyclopentylmethyl]-butyric acid tert-butyl ester - 69198 3.4.24.11 4-methoxy-2-[1-[(trans-2-(4-fluorophenyl)-cyclopropylcarbamoyl)]-cyclopentylmethyl]-butyric acid tert-butyl ester - 67984 3.4.24.11 4-methoxy-2-[1-[(trans-2-(4-methoxy-phenyl)-cyclopropylcarbamoyl)]-cyclopentylmethyl]-butyric acid tert-butyl ester - 67985 3.4.24.11 4-methoxy-2-[1-[2-(4-methoxy-phenoxy)-ethylcarbamoyl]-cyclopentylmethyl]-butyric acid tert-butyl ester - 67986 3.4.24.11 4-methoxy-2-[1-[2-(4-methoxy-phenyl)-ethylcarbamoyl]-cyclopentylmethyl]-butyric acid tert-butyl ester - 67987 3.4.24.11 4-methoxy-2-[1-[3-(4-methoxy-phenyl)-propylcarbamoyl]-cyclopentylmethyl]-butyric acid tert-butyl ester - 67988 3.4.24.11 6-(biphenyl-4-yl)-2-(4-bromobenzyl)-4-oxo-5-sulfanylhexanoic acid - 238570 3.4.24.11 6-[4-[(1-acetylpiperidin-4-yl)(sulfanyl)methyl]phenyl]-2-(4-bromobenzyl)-4-oxo-5-sulfanylhexanoic acid - 238578 3.4.24.11 6-[4-[(1-benzoylpiperidin-4-yl)(sulfanyl)methyl]phenyl]-2-(4-bromobenzyl)-4-oxo-5-sulfanylhexanoic acid - 238579 3.4.24.11 6-[4-[(1-benzylpiperidin-4-yl)(sulfanyl)methyl]phenyl]-2-(4-bromobenzyl)-4-oxo-5-sulfanylhexanoic acid - 238580 3.4.24.11 6-[4-[cyclohexyl(sulfanyl)methyl]phenyl]-4-oxo-5-sulfanyl-2-[4-(thiophen-3-yl)benzyl]hexanoic acid - 238581 3.4.24.11 Acetorphan - 29667 3.4.24.11 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 160189 3.4.24.11 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 7695 3.4.24.11 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 7695 3.4.24.11 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 62342 3.4.24.11 angiotensin I - 690 3.4.24.11 atrial natriuretic factor - 16266 3.4.24.11 bradykinin - 466 3.4.24.11 Butanedione - 5135 3.4.24.11 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 151791 3.4.24.11 candoxatrilat application restores vagal reflex bradycardia in old rats to levels similar to those in young neutral endopeptidase inhibitor-treated rats 75481 3.4.24.11 candoxatrilat - 75481 3.4.24.11 CGS24592 - 144015 3.4.24.11 chymostatin - 511 3.4.24.11 cis-4-[([1-[(2S)-2-carboxy-3-(2-methoxyethoxy)propyl]cyclopentyl]carbonyl)amino]cyclohexanecarboxylic acid - 86790 3.4.24.11 diethyl dicarbonate - 463 3.4.24.11 diisopropyl fluorophosphate - 244 3.4.24.11 dithiothreitol weak 45 3.4.24.11 dithiothreitol - 45 3.4.24.11 DL-[N-(3-mercapto-2-benzylpropanoyl)]glycine following neprilysin inhibition, islet amyloid deposition and beta-cell apoptosis increase by 54 and 75%, respectively 160188 3.4.24.11 EDTA - 21 3.4.24.11 EDTA complete inhibition 21 3.4.24.11 EGTA - 173 3.4.24.11 fasidotrilat fasidotrilat interacts with the Arg664 of hNEP with more consistent bidentate hydrogen bonding and with the His658 with monodentate hydrogen bonding 38310 3.4.24.11 GSH - 142 3.4.24.11 heparin - 227 3.4.24.11 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 33 3.4.24.11 Insulin B chain inhibits the activity with substrate N-(4-carboxy-1-oxobutyl)-L-alanyl-L-alanyl-N-(4-methoxy-2-naphthalenyl)-L-phenylalaninamide 10673 3.4.24.11 L-Cys - 336 3.4.24.11 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 160190 3.4.24.11 Leu5-enkephalin - 4615 3.4.24.11 Leu5-enkephalin hydrolysis of succinyl-Ala-Ala-Phe-4-methylcoumarin 7-amide 4615 3.4.24.11 MCB3937 bifunctional inhibitor of NEP and DPP-IV 25035 3.4.24.11 MCB4241 bifunctional inhibitor of NEP and DPP-IV 69197 3.4.24.11 Met5-enkephalin - 4902 3.4.24.11 Met5-enkephalin hydrolysis of succinyl-Ala-Ala-Phe-4-methylcoumarin 7-amide 4902 3.4.24.11 additional information proteins derived from the Tat protein of HIV 2 3.4.24.11 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 2 3.4.24.11 additional information application of aldosterone, atrial natriuretic peptide, asymmetric dimethylarginine, and angiotensin peptides fail to cause down-regulation of renal neprilysin expression in vitro 2 3.4.24.11 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 2 3.4.24.11 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 2 3.4.24.11 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 2 3.4.24.11 additional information molecular docking studies, overview. For substrate and inhibitor binding, Arg664 and Zn697 are identified as the most conserved residues 2 3.4.24.11 N-(2-benzyl-3-sulfanylpropanoyl)glycine synthetic NEP inhibitor 160187 3.4.24.11 N-(2-benzyl-4-oxo-6-phenyl-5-sulfanylhexanoyl)-L-alanine - 238744 3.4.24.11 N-(2-benzyl-4-oxo-6-phenyl-5-sulfanylhexanoyl)-L-tryptophan - 238745 3.4.24.11 N-([1-[(2S)-2-carboxy-3-[[N2-(methylsulfonyl)-L-lysyl]amino]propyl]cyclopentyl]carbonyl)-L-tyrosine - 86791 3.4.24.11 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 206288 3.4.24.11 N-[(2RS)-3-hydroxyaminocarbonyl-2-benzyl-1-oxopropyl]-Gly - 47366 3.4.24.11 N-[(2S)-3-phenyl-2-(sulfanylmethyl)propanoyl]-L-tryptophan - 240091 3.4.24.11 N-[1(R,S)-carboxy-2-phenylethyl]-Phe-p-aminobenzoate - 100965 3.4.24.11 N-[2-(4-bromobenzyl)-4-oxo-5-phenyl-5-sulfanylpentanoyl]-L-alanine - 239001 3.4.24.11 N-[2-(4-bromobenzyl)-4-oxo-5-sulfanylhexanoyl]-L-tryptophan - 239002 3.4.24.11 N-[2-(4-bromobenzyl)-4-oxo-6-phenyl-5-sulfanylhexanoyl]-L-alanine - 239003 3.4.24.11 N-[2-(4-bromobenzyl)-4-oxo-6-phenyl-5-sulfanylhexanoyl]-L-tryptophan - 239004 3.4.24.11 N-[2-(4-bromobenzyl)-6-methyl-4-oxo-5-sulfanyloctanoyl]-L-alanine - 239005 3.4.24.11 N-[2-(biphenyl-4-ylmethyl)-4-oxo-5-sulfanylhexanoyl]-L-alanine - 239007 3.4.24.11 N-[2-(biphenyl-4-ylmethyl)-4-oxo-6-phenyl-5-sulfanylhexanoyl]-L-alanine - 239008 3.4.24.11 N-[2-(biphenyl-4-ylmethyl)-6-methyl-4-oxo-5-sulfanyloctanoyl]-L-alanine - 239009 3.4.24.11 N-[2-benzyl-6-(4-bromophenyl)-4-oxo-5-sulfanylhexanoyl]-L-leucine - 239014 3.4.24.11 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 100992 3.4.24.11 N-[N-[1(5)-carboxy-3-(4-hydroxyphenyl)propyl]-(5)-phenylalanyl]-(5)-isoserine - 100993 3.4.24.11 NaCl brain enzyme; lung enzyme 42 3.4.24.11 NaCl no inhibition of the enzyme from brain and kidney 42 3.4.24.11 NaCl brain enzyme 42 3.4.24.11 neurotensin - 2209 3.4.24.11 omapatrilat - 25945 3.4.24.11 opiorphin - 160185 3.4.24.11 pepstatin - 396 3.4.24.11 Phe-Gly - 5600 3.4.24.11 Phe-Trp - 47455 3.4.24.11 Phenylglyoxal - 301 3.4.24.11 phosphate - 16 3.4.24.11 phosphoramidon - 645 3.4.24.11 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 645 3.4.24.11 phosphoramidon synthetic NEP inhibitor 645 3.4.24.11 phosphoramidon the inhibitor induces a dramatic increase in amyloid-beta peptide levels 645 3.4.24.11 phosphoramidon a typical inhibitor for metalloproteinase 645 3.4.24.11 phosphoramidon strong, consistent interactions with Arg664, Glu531 and His658 of hNEP 645 3.4.24.11 phosphoramidon partial 645 3.4.24.11 PMSF weak inhibition 248 3.4.24.11 puromycin - 657 3.4.24.11 sacubitril - 239140 3.4.24.11 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 239141 3.4.24.11 SCH39370 - 101443 3.4.24.11 SCH48446 i.e. the diiodo analog of N-[N-[1(5)-carboxy-3-(4-hydroxyphenyl)propyl]-(5)-phenylalanyl]-(5)-isoserine 101444 3.4.24.11 sialorphin opiorphin homologue inhibits NEP 160186 3.4.24.11 SQ 28603 - 97539 3.4.24.11 Substance P - 1259 3.4.24.11 Tat peptide 5118 - 18681 3.4.24.11 tert-butyl 2-([1-[(5-benzyl-1,3,4-thiadiazol-2-yl)carbamoyl]cyclopentyl]methyl)-4-methoxybutanoate - 69481 3.4.24.11 thiol kidney enzyme; lung enzyme 2763 3.4.24.11 thiol lung enzyme 2763 3.4.24.11 thiol kidney enzyme 2763 3.4.24.11 thiol brain enzyme 2763 3.4.24.11 thiol intestine enzyme; kidney enzyme 2763 3.4.24.11 thiorphan - 1128 3.4.24.11 thiorphan 1 mM, completely blocks neutral endopeptidase activity 1128 3.4.24.11 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 1128 3.4.24.11 thiorphan thiorphan eliminates proteolysis of the alpha-subunit 1128 3.4.24.11 thiorphan the inhibitor induces a dramatic increase in amyloid-beta peptide levels 1128 3.4.24.11 thiorphan complete inhibition 1128 3.4.24.11 thiorphan Arg49 and Arg664 act to support the ligand binding in NEP 1128 3.4.24.11 thiorphan a NEP-specific inhibitor 1128 3.4.24.11 thiorphan weak 1128 3.4.24.11 thiorphan-NH2 - 31656 3.4.24.11 tris(2-carboxyethyl)phosphine TCEP, strong inhibition 37311 3.4.24.11 U46619 a thromboxane mimetic 66987 3.4.24.11 UK-69,578 - 101696 3.4.24.11 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 160184 3.4.24.11 valsartan - 160184 3.4.24.11 Z-Leu-Leu-Leu-H - 206287