| Size | Price | Stock | Qty |
|---|---|---|---|
| 5mg |
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| 1g | |||
| Other Sizes |
| Targets |
Nesiritide targets natriuretic peptide receptors, with Kd values of 7.3 pM for NPR-A and 13 pM for NPR-C. Human BNP binds to the particulate guanylate cyclase receptor of vascular smooth muscle and endothelial cells, leading to increased intracellular concentrations of cGMP. This results in smooth muscle cell relaxation and vasodilation. The physiological actions of BNP are similar to those of ANP and include a decrease in systemic vascular resistance and central venous pressure as well as an increase in natriuresis. Nesiritide also reduces the renin-angiotensin system (RAS) and sympathetic nerve activity. It binds to NPR-B with 10-fold lower affinity than to NPR-A.
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| ln Vitro |
In vitro, nesiritide acetate has been shown to increase the production of cGMP in vascular smooth muscle and endothelial cells. The compound has a clear expansion effect on small arteries and venules throughout the body. It can significantly reduce pulmonary capillary wedge pressure and right atrial pressure, thereby reducing the preload of the heart in heart failure. Nesiritide also significantly reduces total peripheral vascular resistance, thereby reducing cardiac afterload in heart failure. The compound has the effect of increasing the cardiac index, and its mechanism is related to reducing cardiac afterload. It has a specific dilatation effect on coronary arteries and reduces myocardial oxygen consumption.
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| ln Vivo |
In vivo, nesiritide acetate exhibits hemodynamic benefits in patients with acute decompensated heart failure. It decreases systemic vascular resistance and central venous pressure while increasing natriuresis. The compound improves cardiac index by reducing both preload and afterload. Nesiritide inhibits angiotensin II-induced increases in blood pressure. It facilitates cardiovascular fluid homeostasis through counterregulation of the renin-angiotensin-aldosterone system. Clinical studies have demonstrated that nesiritide improves symptoms of dyspnea and reduces hospitalization time in heart failure patients. The compound's lipolytic effects contribute to fatty acid mobilization in congestive heart failure.
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| Enzyme Assay |
For in vitro receptor binding assays, nesiritide acetate is evaluated using cell-free systems to assess its affinity for natriuretic peptide receptors. Radioligand binding assays are performed using membrane preparations from cells expressing NPR-A, NPR-B, or NPR-C. Competitive binding experiments with radiolabeled BNP or specific ligands allow determination of Kd values. Scatchard analysis is used to calculate receptor binding affinity and receptor density. Binding specificity is assessed using receptor-selective competitors. cGMP production assays using purified guanylate cyclase or cell membranes can also be performed to evaluate receptor activation. These cell-free assays help characterize nesiritide's receptor binding profile and identify the molecular determinants of receptor recognition.
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| Cell Assay |
In vitro cellular assays for nesiritide acetate are performed using cells expressing natriuretic peptide receptors. Vascular smooth muscle cells and endothelial cells are commonly used. Cells are cultured in appropriate media and treated with nesiritide at various concentrations. Intracellular cGMP levels are measured using ELISA or radioimmunoassay as a readout of receptor activation. Vasorelaxation can be assessed using isolated blood vessel preparations in organ baths. Inhibition of angiotensin II-induced vasoconstriction can also be studied in vascular smooth muscle cells. ERK1/2 phosphorylation and other downstream signaling events are assessed by Western blotting. Cell proliferation and migration assays may be performed to study the compound's effects on vascular remodeling.
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| Animal Protocol |
In vivo animal experiments with nesiritide acetate are conducted to study its cardiovascular effects. Rodent models of heart failure, such as myocardial infarction-induced or pressure overload-induced models, are commonly used. Nesiritide is administered via intravenous infusion or bolus injection. Hemodynamic parameters including blood pressure, heart rate, cardiac output, and central venous pressure are measured using invasive or non-invasive techniques. Urine output and sodium excretion are measured to assess natriuretic effects. Blood samples are collected for measurement of cGMP, BNP levels, and markers of heart failure. Echocardiography may be performed to assess cardiac function. Tissue samples can be harvested for histological analysis and molecular studies.
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| ADME/Pharmacokinetics |
Pharmacokinetic properties of nesiritide acetate are characteristic of peptide therapeutics. The compound has a molecular weight of 3506.07 and the chemical formula C145H246N50O43S4. It is soluble in water at ≥40 mg/mL and should be stored at -20°C, protected from light. As a peptide, nesiritide is not orally bioavailable and must be administered intravenously. The compound has a short half-life in circulation due to rapid enzymatic degradation and clearance. It is metabolized primarily by neutral endopeptidase and other peptidases. Renal clearance contributes to elimination. Protein binding is moderate. The compound is unstable in solutions and freshly prepared solutions are recommended.
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| Toxicity/Toxicokinetics |
The toxicological profile of nesiritide acetate is primarily related to its hemodynamic effects. Excessive vasodilation can lead to hypotension, which is the most common adverse effect. Other potential adverse effects include headache, nausea, and renal function changes. The compound should be used with caution in patients with hypotension, aortic stenosis, or other conditions where vasodilation may be detrimental. Nesiritide is contraindicated in patients with hypersensitivity to the drug or its components. The compound is for research use and clinical applications require appropriate medical supervision. Safety assessments in animal models have been conducted to establish the therapeutic index and identify potential toxicities.
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| Additional Infomation |
A peptide secreted by the brain and atria, primarily stored in the ventricular myocardium. It induces sodium excretion, diuresis, vasodilation, and inhibits the secretion of renin and aldosterone. It can improve cardiac function. It contains 32 amino acids.
See also: Brain natriuretic peptide (note moved to). Nesiritide acetate is clinically approved for the treatment of acutely decompensated congestive heart failure. It represents a significant advancement in the management of heart failure as a recombinant BNP therapeutic. The compound's mechanism of action through natriuretic peptide receptor activation and cGMP production has been extensively studied and validated. Nesiritide is used to investigate the pathophysiology of heart failure and the role of the natriuretic peptide system in cardiovascular homeostasis. It serves as a tool for studying the counterregulation of the renin-angiotensin-aldosterone system and sympathetic nervous system. The compound is also valuable for research into cardiac biomarker development, as BNP levels are used clinically for heart failure diagnosis and prognosis. |
| Molecular Formula |
C143H244N50O42S4
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|---|---|
| Exact Mass |
3461.74
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| CAS # |
114471-18-0
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| PubChem CID |
71306940
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| Appearance |
White to off-white solid powder
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| Density |
1.529 g/cm3
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| Index of Refraction |
1.679
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| Hydrogen Bond Donor Count |
57
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| Hydrogen Bond Acceptor Count |
57
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| Rotatable Bond Count |
115
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| Heavy Atom Count |
243
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| Complexity |
7780
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| Defined Atom Stereocenter Count |
28
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| SMILES |
NCCCC[C@@H]1NC(=O)[C@H](CCCNC(=N)N)NC(=O)CNC(=O)[C@H](CC2=CC=CC=C2)NC(=O)[C@@H](NC(CNC([C@@H](NC(CNC([C@@H](NC([C@@H](NC([C@@H](NC([C@@H](NC([C@@H]2CCCN2C([C@H](CO)N)=O)=O)CCCCN)=O)CCSC)=O)C(C)C)=O)CCC(=O)N)=O)=O)CO)=O)=O)CSSC[C@@H](C(N[C@H](C(N[C@H](C(N[C@H](C(N[C@H](C(N[C@H](C(N[C@@H](CC2=CN=CN2)C(=O)O)=O)CCCNC(=N)N)=O)CCCNC(=N)N)=O)CC(C)C)=O)C(C)C)=O)CCCCN)=O)NC(=O)CNC(=O)[C@H](CC(C)C)NC(=O)CNC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@H]([C@H](CC)C)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](CCSC)NC1=O
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| InChi Key |
FJULFJFRGUHITK-INJFIXSDSA-N
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| InChi Code |
InChI=1S/C143H244N50O42S4.C2H4O2/c1-13-76(10)112(137(232)180-86(36-26-48-161-143(155)156)122(217)183-93(56-109(206)207)128(223)178-88(40-50-236-11)124(219)173-81(30-17-20-42-144)119(214)174-83(32-19-22-44-146)125(220)190-111(75(8)9)136(231)184-91(53-73(4)5)127(222)176-84(34-24-46-159-141(151)152)121(216)175-85(35-25-47-160-142(153)154)123(218)185-94(139(234)235)55-78-57-157-71-167-78)192-132(227)99(68-199)188-131(226)98(67-198)187-130(225)97(66-197)186-129(224)96(65-196)171-107(204)61-163-114(209)90(52-72(2)3)169-105(202)59-166-117(212)100-69-238-239-70-101(133(228)182-92(54-77-28-15-14-16-29-77)115(210)164-58-104(201)168-80(118(213)189-100)33-23-45-158-140(149)150)172-108(205)62-165-116(211)95(64-195)170-106(203)60-162-113(208)87(38-39-103(148)200)181-135(230)110(74(6)7)191-126(221)89(41-51-237-12)177-120(215)82(31-18-21-43-145)179-134(229)102-37-27-49-193(102)138(233)79(147)63-194;1-2(3)4/h14-16,28-29,57,71-76,79-102,110-112,194-199H,13,17-27,30-56,58-70,144-147H2,1-12H3,(H2,148,200)(H,157,167)(H,162,208)(H,163,209)(H,164,210)(H,165,211)(H,166,212)(H,168,201)(H,169,202)(H,170,203)(H,171,204)(H,172,205)(H,173,219)(H,174,214)(H,175,216)(H,176,222)(H,177,215)(H,178,223)(H,179,229)(H,180,232)(H,181,230)(H,182,228)(H,183,217)(H,184,231)(H,185,218)(H,186,224)(H,187,225)(H,188,226)(H,189,213)(H,190,220)(H,191,221)(H,192,227)(H,206,207)(H,234,235)(H4,149,150,158)(H4,151,152,159)(H4,153,154,160)(H4,155,156,161);1H3,(H,3,4)/t76-,79-,80-,81-,82-,83-,84-,85-,86-,87-,88-,89-,90-,91-,92-,93-,94-,95-,96-,97-,98-,99-,100-,101-,102-,110-,111-,112-;/m0./s1
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| Chemical Name |
acetic acid;(3S)-3-[[(2S)-2-[[(2S,3S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[2-[[(2S)-2-[[2-[[(4R,7S,13S,16R)-16-[[2-[[(2S)-2-[[2-[[(2S)-5-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-6-amino-2-[[(2S)-1-[(2S)-2-amino-3-hydroxypropanoyl]pyrrolidine-2-carbonyl]amino]hexanoyl]amino]-4-methylsulfanylbutanoyl]amino]-3-methylbutanoyl]amino]-5-oxopentanoyl]amino]acetyl]amino]-3-hydroxypropanoyl]amino]acetyl]amino]-13-benzyl-7-(3-carbamimidamidopropyl)-6,9,12,15-tetraoxo-1,2-dithia-5,8,11,14-tetrazacycloheptadecane-4-carbonyl]amino]acetyl]amino]-4-methylpentanoyl]amino]acetyl]amino]-3-hydroxypropanoyl]amino]-3-hydroxypropanoyl]amino]-3-hydroxypropanoyl]amino]-3-hydroxypropanoyl]amino]-3-methylpentanoyl]amino]-5-carbamimidamidopentanoyl]amino]-4-[[(2S)-1-[[(2S)-6-amino-1-[[(2S)-6-amino-1-[[(2S)-1-[[(2S)-1-[[(2S)-5-carbamimidamido-1-[[(2S)-5-carbamimidamido-1-[[(1S)-1-carboxy-2-(1H-imidazol-4-yl)ethyl]amino]-1-oxopentan-2-yl]amino]-1-oxopentan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-3-methyl-1-oxobutan-2-yl]amino]-1-oxohexan-2-yl]amino]-1-oxohexan-2-yl]amino]-4-methylsulfanyl-1-oxobutan-2-yl]amino]-4-oxobutanoic acid
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
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| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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