DT-Web

DB04899 - Nesiritide


Identification
Name Nesiritide
Accession Number DB04899
Type biotech
Description Nesiritide is a medication used to treat acutely decompensated congestive heart failure with dyspnea at rest or with minimal exertion (such as talk, eating or bathing). Nesiritide is the recombinant form of the 32 amino acid human B-type natriuretic peptide, which is normally produced by the ventricular myocardium.
Structure
MOL SDF PDB SMILES InChI
Categories (*)
Molecular Weight 3464.0000
Groups approved
Monoisotopic Weight Not Available
Pharmacology
Indication For the intravenous treatment of patients with acutely decompensated congestive heart failure who have dyspnea at rest or with minimal activity.
Mechanism of action Human BNP binds to the particulate guanylate cyclase receptor of vascular smooth muscle and endothelial cells, leading to increased intracellular concentrations of guanosine 3'5'-cyclic monophosphate (cGMP) and smooth muscle cell relaxation. Cyclic GMP serves as a second messenger to dilate veins and arteries. Nesiritide has been shown to relax isolated human arterial and venous tissue preparations that were precontracted with either endothelin-1 or the alpha-adrenergic agonist, phenylephrine. In human studies, nesiritide produced dose-dependent reductions in pulmonary capillary wedge pressure (PCWP) and systemic arterial pressure in patients with heart failure. In animals, nesiritide had no effects on cardiac contractility or on measures of cardiac electrophysiology such as atrial and ventricular effective refractory times or atrioventricular node conduction. Naturally occurring atrial natriuretic peptide (ANP), a related peptide, increases vascular permeability in animals and humans and may reduce intravascular volume. The effect of nesiritide on vascular permeability has not been studied.
Absorption Administration of nesiritide exhibits biphasic disposition from the plasma.
Protein binding Not Available
Biotransformation Nesiritide undergoes proteolytic cleavage of the peptide by endopeptidases, such as neutral endopeptidase, which are present on the vascular lumenal surface.
Route of elimination Human BNP is cleared from the circulation via the following three independent mechanisms, in order of decreasing importance: 1) binding to cell surface clearance receptors with subsequent cellular internalization and lysosomal proteolysis; 2) proteolytic cleavage of the peptide by endopeptidases, such as neutral endopeptidase, which are present on the vascular lumenal surface; and 3) renal filtration.
Toxicity No data are available with respect to overdosage in humans. The expected reaction would be excessive hypotension, which should be treated with drug discontinuation or reduction and appropriate measures.
Affected organisms
  • Humans and other mammals
Interactions
Drug Interactions
Drug Mechanism of interaction
Treprostinil Additive hypotensive effect. Monitor antihypertensive therapy during concomitant use.
Food Interactions Not Available

Targets


Atrial natriuretic peptide receptor A
Name Atrial natriuretic peptide receptor A
Gene Name NPR1
Pharmacological action unknown
Actions binder
References
  • Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. - Pubmed
DTHybrid score 1.4797
Atrial natriuretic peptide receptor B
Name Atrial natriuretic peptide receptor B
Gene Name NPR2
Pharmacological action unknown
Actions Not Available
References Not Available
DTHybrid score 1.3973
Atrial natriuretic peptide clearance receptor
Name Atrial natriuretic peptide clearance receptor
Gene Name NPR3
Pharmacological action unknown
Actions Not Available
References Not Available
DTHybrid score 0.7503

Predictions


Id Partner name Gene Name Score
147 Aldehyde dehydrogenase, mitochondrial ALDH2 0.1854
6024 Cytochrome P450 1A1 CYP1A1 0.0368
6013 Cytochrome P450 2E1 CYP2E1 0.0346
4200 Cytochrome P450 1A2 CYP1A2 0.0304
4512 Cytochrome P450 3A4 CYP3A4 0.0258
1052 Cytotoxic T-lymphocyte protein 4 CTLA4 0.0148
4878 Glycoprotein hormones alpha chain CGA 0.0148
4882 Dipeptidyl aminopeptidase-like protein 6 DPP6 0.0148
1072 Granzyme B GZMB 0.0148
4880 Membrane cofactor protein CD46 0.0148
4877 Beta-mannanase man 0.0148
4871 Endo-beta-N-acetylglucosaminidase F3 endOF3 0.0148
4856 CD209 antigen CD209 0.0148
1354 Beta-glucuronidase GUSB 0.0148
4889 Ig epsilon chain C region IGHE 0.0148
4869 Major capsid protein A430L 0.0148
4852 Reticulon-4 receptor RTN4R 0.0148
757 Fusion glycoprotein F0 F 0.0148
4875 Fusion glycoprotein F0 F 0.0148
4850 Beta-2-glycoprotein 1 APOH 0.0148
1563 Platelet glycoprotein Ib alpha chain GP1BA 0.0148
442 Envelope glycoprotein gp41 0.0148
4859 Envelope glycoprotein env 0.0148
4189 Alpha-galactosidase A GLA 0.0148
3352 Structural polyprotein Not Available 0.0148
3628 Structural polyprotein Not Available 0.0148
4892 Structural polyprotein Not Available 0.0148
4845 ADAM 33 ADAM33 0.0148
4721 Beta-1,4-mannanase manA 0.0148
1184 Interferon beta IFNB1 0.0129
6858 Inactive carboxylesterase 4 CES1P1 0.0129
4857 Zinc-alpha-2-glycoprotein AZGP1 0.0129
4861 Interleukin-6 receptor alpha chain IL6R 0.0129
1379 Interleukin-12 subunit beta IL12B 0.0129
793 T-cell surface antigen CD2 CD2 0.0129
4890 Hemagglutinin HA 0.0129
6566 Hemagglutinin Not Available 0.0129
119 Carcinoembryonic antigen-related cell adhesion molecule 1 CEACAM1 0.0129
554 Low-density lipoprotein receptor LDLR 0.0129
3837 Cytokine receptor common beta chain CSF2RB 0.0129
3444 Cyanovirin-N Not Available 0.0119
18 High affinity immunoglobulin epsilon receptor subunit alpha FCER1A 0.0119
1859 Prostatic acid phosphatase ACPP 0.0119
2998 Sialic acid-binding Ig-like lectin 7 SIGLEC7 0.0119
852 Heparin cofactor 2 SERPIND1 0.0119
3258 Mannosyl-oligosaccharide alpha-1,2-mannosidase MSDC 0.0119
3140 Hemagglutinin-neuraminidase HN 0.0119
3609 Hemagglutinin-neuraminidase HN 0.0119
6120 Cation-independent mannose-6-phosphate receptor IGF2R 0.0119
2297 Genome polyprotein Not Available 0.0119
2322 Genome polyprotein Not Available 0.0119
2694 Genome polyprotein Not Available 0.0119
2719 Genome polyprotein Not Available 0.0119
2860 Genome polyprotein Not Available 0.0119
2928 Genome polyprotein Not Available 0.0119
3160 Genome polyprotein Not Available 0.0119
3260 Genome polyprotein Not Available 0.0119
4783 Genome polyprotein Not Available 0.0119
5726 Genome polyprotein Not Available 0.0119
5779 Genome polyprotein Not Available 0.0119
5867 Genome polyprotein Not Available 0.0119
6253 Genome polyprotein Not Available 0.0119
6301 Genome polyprotein Not Available 0.0119
6380 Genome polyprotein Not Available 0.0119
6381 Genome polyprotein Not Available 0.0119
6437 Genome polyprotein Not Available 0.0119
6520 Genome polyprotein Not Available 0.0119
6521 Genome polyprotein Not Available 0.0119
6652 Genome polyprotein Not Available 0.0119
6734 Genome polyprotein Not Available 0.0119
6735 Genome polyprotein Not Available 0.0119
6736 Genome polyprotein Not Available 0.0119
6737 Genome polyprotein Not Available 0.0119
6738 Genome polyprotein Not Available 0.0119
6739 Genome polyprotein Not Available 0.0119
6744 Genome polyprotein Not Available 0.0119
6748 Genome polyprotein Not Available 0.0119
6894 Genome polyprotein Not Available 0.0119
6898 Genome polyprotein Not Available 0.0119
4666 Fucose-binding lectin PA-IIL lecB 0.0112
2372 Bifunctional tail protein 9 0.0112
4787 Envelope glycoprotein gp160 env 0.0112
4820 Envelope glycoprotein gp160 env 0.0112
5727 Envelope glycoprotein gp160 env 0.0112
2577 Endoplasmic reticulum mannosyl-oligosaccharide 1,2-alpha-mannosidase MAN1B1 0.0107
64 Neuraminidase NA 0.0104
641 Neuraminidase NA 0.0104
2676 Neuraminidase NA 0.0104
3026 Neuraminidase NA 0.0104
3519 Neuraminidase NA 0.0104
6007 Neuraminidase NA 0.0104
3480 Mannan endo-1,4-beta-mannosidase manA 0.0104
595 Fibrinogen alpha chain FGA 0.0103
1782 Neutrophil gelatinase-associated lipocalin LCN2 0.0101
1439 Lactotransferrin LTF 0.01
1243 Cathepsin D CTSD 0.0098
2430 Chondroitinase B cslB 0.0095
958 Insulin-like growth factor 1 receptor IGF1R 0.0095
2581 Chondroitinase AC cslA 0.0093
309 Antithrombin-III SERPINC1 0.0093
6307 Ig gamma-2 chain C region IGHG2 0.0093
6847 Lactase-phlorizin hydrolase LCT 0.0093
6500 Phospholipase A2 PLA2G1B 0.009
2207 Rhodopsin RHO 0.0087
3814 Complement C1r subcomponent C1R 0.0082
4604 Liver carboxylesterase 1 CES1 0.0078
4785 Ig gamma-1 chain C region IGHG1 0.0078
76 Nitric-oxide synthase, brain NOS1 0.0077
952 Dipeptidyl peptidase 4 DPP4 0.0067
3923 Cholinesterase BCHE 0.0064
20 Prostaglandin G/H synthase 1 PTGS1 0.0059
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