Nesiritide, also known as Brain Natriuretic Peptide-32 human, is an agonist of the natriuretic peptide receptor (NPR), with Kd values of 7.3 pM for NPR-A and 13 pM for NPR-C [1]. While ProBNP1-108 is 13 times less powerful than Nesiritide (BNP1-32), it nevertheless stimulates guanylate cyclase-A (GC-A) to almost maximal activity. Nesiritide binds to human GC-A 35 times more strongly than ProBNP1-108. Nesiritide and proBNP1-108 do not activate GC-B. Compared to nesiritide, the binding strength of natriuretic peptide scavenging receptors to proBNP1-108 is three times lower. When degraded by human renal membrane, proBNP1-108 has a half-life that is 2.7 times longer than that of nesiritide and a complete degradation period that is 6 times longer. The first-order and second-order exponential decay models are best fitted by nesiritide and proBNP1-108, respectively [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]

---

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

---

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.

---

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

---

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

56

55

91

239

7750

28

CC[C@@H]([C@H]1C(N[C@H](C(N[C@H](C(N[C@H](C(N[C@H](C(NCC(N[C@H](C(NCC(N[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](C(O)=O)CC2=CN=CN2)=O)CCCNC(N)=N)=O)CCCNC(N)=N)=O)CC(C)C)=O)C(C)C)=O)CCCCN)=O)CSSC[C@H](NC(CNC([C@@H](NC(CNC([C@@H](NC([C@@H](NC([C@@H](NC([C@@H](NC([C@@H]3CCCN3C([C@@H](N)CO)=O)=O)CCCCN)=O)CCSC)=O)C(C)C)=O)CCC(N)=O)=O)=O)CO)=O)=O)C(N[C@H](C(NCC(N[C@H](C(N[C@H](C(N[C@H](C(N[C@H](C(N[C@H](C(N1)=O)CCCNC(N)=N)=O)CC(O)=O)=O)CCSC)=O)CCCCN)=O)CCCNC(N)=N)=O)=O)CC4=CC=CC=C4)=O)=O)=O)CC(C)C)=O)=O)CO)=O)CO)=O)CO)=O)CO)=O)C

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

Note: Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture and light.

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)

Solubility in Formulation 1: 100 mg/mL (28.87 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with sonication.

---

 (Please use freshly prepared in vivo formulations for optimal results.)