Nesiritide   中文名称: 人脑利钠肽

Nesiritide，也称为 Brain Natriuretic Peptide-32 human，是一种利钠肽受体 (NPR) 的激动剂，NPR-A 的 Kd 值为 7.3 pM，NPR-C 的 Kd 值为 13 pM [1]。虽然 ProBNP1-108 的功效比奈西立肽 (BNP1-32) 低 13 倍，但它仍能刺激鸟苷酸环化酶-A (GC-A) 达到几乎最大活性。 Nesiritide 与人 GC-A 的结合强度是 ProBNP1-108 的 35 倍。 Nesiritide 和 proBNP1-108 不会激活 GC-B。与奈西立肽相比，利钠肽清除受体与 proBNP1-108 的结合强度低三倍。当被人肾膜降解时，proBNP1-108的半衰期比奈西立肽长2.7倍，完全降解期长6倍。一阶和二阶指数衰减模型分别最适合奈西立肽和 proBNP1-108 [2]。

Absorption, Distribution and Excretion
Administration of nesiritide exhibits biphasic disposition from the plasma.
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.
0.19 L/kg
9.2 mL/min/k [patients with congestive heart failure receiving IV infusion]

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Metabolism / Metabolites
Nesiritide undergoes proteolytic cleavage of the peptide by endopeptidases, such as neutral endopeptidase, which are present on the vascular lumenal surface.

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Biological Half-Life
Approximately 18 minutes

[1]. Molecular biology of the natriuretic peptides and their receptors. Circulation. 1992 Oct;86(4):1081-8.

[2]. ProBNP(1-108) is resistant to degradation and activates guanylyl cyclase-A with reduced potency. Clin Chem. 2011 Sep;57(9):1272-8.

Nesiritide is a polypeptide.
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 a 32 amino acid recombinant human B-type natriuretic peptide.
Nesiritide is a recombinant version of the cardiac neurohormone, human B-type natriuretic peptide (hBNP) produced by the ventricular myocardium. Nesiritide binds to natriuretic peptide receptors on vascular smooth muscle and endothelial cells, through which it triggers guanylate cyclase dependent signal transduction resulting in increase of intracellular concentrations of cGMP. This leads to smooth muscle cell relaxation causing arterial and venous dilatation.
A PEPTIDE that is secreted by the BRAIN and the HEART ATRIA, stored mainly in cardiac ventricular MYOCARDIUM. It can cause NATRIURESIS; DIURESIS; VASODILATION; and inhibits secretion of RENIN and ALDOSTERONE. It improves heart function. It contains 32 AMINO ACIDS.

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Drug Indication
For the intravenous treatment of patients with acutely decompensated congestive heart failure who have dyspnea at rest or with minimal activity.
FDA Label

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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.

C143H244N50O42S4

3464.05

3461.737

124584-08-3

71308561

White to off-white solid powder

1.5±0.1 g/cm3

1.679

-16.34

1613.94

56

55

91

239

7750

28

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Nesiritide Brain Natriuretic Peptide-32 human

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

注意： 请将本产品存放在密封且受保护的环境中（例如氮气保护），避免吸湿/受潮和光照。

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

H2O : ≥ 40 mg/mL (~11.55 mM)

配方 1 中的溶解度: 100 mg/mL (28.87 mM) in PBS (这些助溶剂从左到右依次添加，逐一添加), 澄清溶液; 超声助溶。

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请根据您的实验动物和给药方式选择适当的溶解配方/方案：
1、请先配制澄清的储备液(如：用DMSO配置50 或 100 mg/mL母液(储备液));
2、取适量母液，按从左到右的顺序依次添加助溶剂，澄清后再加入下一助溶剂。以 下列配方为例说明 (注意此配方只用于说明，并不一定代表此产品 的实际溶解配方):
10% DMSO → 40% PEG300 → 5% Tween-80 → 45% ddH2O (或 saline);
假设最终工作液的体积为 1 mL, 浓度为5 mg/mL: 取 100 μL 50 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中，混合均匀/澄清；向上述体系中加入50 μL Tween-80，混合均匀/澄清；然后继续加入450 μL ddH2O (或 saline)定容至 1 mL；
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7、 以上所有助溶剂都可在 Invivochem.cn网站购买。