Neprilysin
Neprilysin (NEP) is currently a focus of interest in cardiovascular medicine because of the impressive benefits of combining NEP inhibition and angiotensin 2 type 1 receptor blockade, demonstrated in the PARADIGM-HF. The gene encoding human NEP is on chromosome 3 (3q21-27); it spans >80 kb and contains 24 exons. NEP is an integral type II, membrane-bound, zinc-dependent endopeptidase composed of 749 amino-acid residues. NEP is found in epithelia, fibroblasts, and neutrophils and in soluble form in the circulation, urine, and cerebrospinal fluid (CSF). In the circulation, NEP is a soluble circulating enzyme, and it is also present on the plasma membranes of neutrophils, where it may cleave the chemotactic peptide fMet-Leu-Phe and modulate the chemotactic response of neutrophils. Soluble neprilysin (sNEP) in blood, urine, and CSF retains catalytic activity, as demonstrated by assays of plasma NEP activity. NEP is expressed in cardiac fibroblasts and cardiomyocytes, and it appears to be more important than angiotensin-converting enzyme (ACE) in clearance of cardiac bradykinin. The distribution of NEP, coupled with the many established and candidate substrates of the enzyme, point to potential roles in multiple organ systems in health and disease. The NPs atrial natriuretic peptide (ANP) and B-type natriuretic peptide (BNP) are of predominantly cardiac origin, whereas C-type natriuretic peptide (CNP) is largely sourced from endothelial cells throughout the systemic vasculature. NEP is responsible for the initial proteolytic cleavage of ANP and CNP. In humans, BNP is relatively resistant to degradation by NEP.
References
1.Bayes-Genis A,et al. J Am Coll Cardiol. 2016;68(6):639–653.
References
1.Bayes-Genis A,et al. J Am Coll Cardiol. 2016;68(6):639–653.
Metabolic Enzyme/Protease
11β-HSD(15)
15-PGDH(1)
ACC(10)
ACE(11)
AChE(29)
Adenylate Cyclase(12)
ALDH(14)
Aldose Reductase(5)
Aminopeptidase(17)
BACE(18)
Casein Kinase(41)
CAT(5)
Cathepsin(9)
CETP(10)
COMT(2)
CPG2(1)
CYPs(6)
Decarboxylase(3)
Dehydrogenase(87)
DGAT(4)
Dopamine beta-hydroxylase(2)
DPP(27)
Elastase(6)
FAAH(19)
Factor Xa(24)
Fatty Acid Synthase(16)
Ftase(2)
FXR(22)
Glucokinase(1)
GSNOR(2)
Guanylate Cyclase(9)
HMGCR(17)
IDH(7)
IDO(19)
IMPDH(2)
LDH(2)
LDL(5)
Lipase(13)
Lipid(9)
Lipoxygenase(0)
MAGL(3)
MAO(52)
MMP(53)
NAMPT(7)
Neprilysin(6)
NKCC(0)
Other Targets(9)
P450(87)
PAI-1(7)
Phosphatase(51)
Phospholipase(42)
PPAR(86)
Protein Phosphatase/PTP(6)
Renin(8)
Retinoid Receptor(23)
SCD(6)
Steroid Sulfatase (STS)(2)
Thioredoxin(1)
TPH(5)
Transferase(24)
Vitamin(39)
Xanthine Oxidase (XAO)(6)
Neprilysin
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Sacubitrilat
catalog no : M22907
cas no: 149709-44-4
Sacubitrilat (LBQ657) is an effective inhibitor of active neprilysin (NEP).Sacubitrilat 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 of 5?nM. -
LHW090-A7
catalog no : M22031
cas no: 1308256-94-1
LHW090-A7 is an neutral endopeptidase (NEP) inhibitor, and an enzyme responsible for the metabolic inactivation of enkephalins. -
LCZ-696
catalog no : M16707
cas no: 936623-90-4
A novel single molecule comprising molecular moieties of valsartan and NEP inhibitor prodrug AHU377. -
Candoxatril
catalog no : M10912
cas no: 123122-55-4
The orally active prodrug of candoxatrilat (UK-73967), potent neutral endopeptidase EC 3.4.24.11 (atriopeptidase) inhibitor. -
Candoxatrilat
catalog no : M10911
cas no: 123122-54-3
A potent neutral endopeptidase EC 3.4.24.11 (atriopeptidase) inhibitor.