Nesiritide Peptide: Structure, Research & Science Guide

By The Peptides Codex Editorial TeamReviewed September 8, 2026

Page data last changed: 2026-10-05. Chemistry registry snapshot: 2026-10-01. Registry refreshes and identity assessments are separate from scientific content review.

Length

n/a

Class

Recombinant natriuretic peptide (natriuretic peptide receptor-A agonist)

Function

Activates the guanylate cyclase receptor NPR-A, raising cGMP in vascular smooth muscle to dilate veins and arteries and promote diuresis

Context

Approved (FDA, 2001) as an intravenous vasodilator for acutely decompensated heart failure; use fell sharply after safety meta-analyses and a large neutral trial

An approved hormone copy whose story is the cautionary one: haemodynamic benefit at launch, safety questions in 2005, and a large trial in 2011 that an NEJM editorial called “the lost decade of nesiritide”.

Also known as: recombinant human B-type natriuretic peptide · rhBNP · Natrecor (brand) · brain natriuretic peptide (recombinant)

Part of the Foundational & therapeutic peptides cluster

Overview

Nesiritide is the recombinant form of human B-type natriuretic peptide (BNP), with an amino-acid sequence identical to the endogenous hormone. It activates the guanylate cyclase receptor NPR-A to relax vascular smooth muscle, dilating veins and arteries and lowering blood pressure, and the FDA approved it in 2001 as an intravenous treatment for acutely decompensated heart failure. Meta-analyses in 2005 raised concerns about renal dysfunction and mortality, and a large 2011 outcomes trial was neutral.

Source & context

Biological / chemical source: Recombinant form of human B-type (brain) natriuretic peptide, identical in sequence to the endogenous hormone

Primary research or clinical context: Approved (FDA, 2001) as an intravenous vasodilator for acutely decompensated heart failure; use fell sharply after safety meta-analyses and a large neutral trial

What nesiritide is

Nesiritide is the recombinant form of human B-type natriuretic peptide, and its amino-acid sequence is identical to that of endogenous human BNP (Dorsch and Rodgers, Pharmacotherapy 2006; IUPHAR record). BNP is one of three structurally related natriuretic hormones: atrial natriuretic peptide (ANP) is secreted from the cardiac atria, BNP from the ventricles, and C-type natriuretic peptide (CNP) mainly stimulates long-bone growth (Potter et al., Handbook of Experimental Pharmacology 2009). PubChem lists nesiritide as compound 71308561, CAS 124584-08-3, and the IUPHAR/BPS Guide to Pharmacology records its FDA approval in 2001 under the brand Natrecor.

Mechanism: the guanylate cyclase receptor

In its natural form BNP binds the guanylate cyclase receptor in vascular smooth muscle and endothelial cells, raising intracellular cyclic GMP and relaxing smooth muscle, which dilates veins and arteries (IUPHAR mechanism record). ANP and BNP both activate the transmembrane guanylyl cyclase natriuretic peptide receptor-A, NPR-A, while CNP activates the related NPR-B (Potter et al. 2009). Administration of nesiritide produces venous and arterial vasodilation and enhanced diuresis (Dorsch and Rodgers 2006). The physiological role of BNP itself is described as acting locally to reduce ventricular fibrosis (Potter et al. 2009).

Early clinical picture

In the years after approval, short-term intravenous infusion of nesiritide was associated with haemodynamic and symptomatic improvements in patients with acutely decompensated congestive heart failure, and reviewers highlighted practical advantages over existing vasodilators, inodilators and inotropes — in particular no apparent pro-arrhythmic effect, and effectiveness in patients on beta-blockers and in those with renal insufficiency (Keating and Goa, Drugs 2003). A 2008 Swiss review grouped it with carvedilol and levosimendan as part of a new hormonal approach to cardiac failure (Fanconi et al., Revue Médicale Suisse 2008).

The safety questions

In 2005 two meta-analyses raised the question of safety, specifically an increased risk of renal dysfunction and mortality with nesiritide therapy, prompting a review titled “Nesiritide: harmful or harmless?” (Dorsch and Rodgers, Pharmacotherapy 2006) and a New England Journal of Medicine exchange headed “Nesiritide — not verified” (Sackner-Bernstein and Aaronson, NEJM 2005). The concerns were not resolved by the existing trials, which had been designed around haemodynamic endpoints rather than outcomes.

The outcomes trial and the “lost decade”

A large randomised outcomes trial published in the New England Journal of Medicine in July 2011 addressed the question directly, and the accompanying editorial by Eric Topol was titled “The lost decade of nesiritide” (Topol, NEJM 2011). The phrase summarises the field's verdict: a decade of use on the strength of haemodynamic surrogates before an adequately powered trial showed no meaningful clinical benefit. A 2018 personal essay, “Nesiritide and Me”, revisits the episode from a cardiologist's perspective (Kittleson, Circulation: Heart Failure 2018). Contemporary heart-failure guidance treats natriuretic peptides primarily as diagnostic biomarkers rather than as therapies (Tsutsui et al., European Journal of Heart Failure 2023).

Nesiritide's timeline as recorded in the cited literature
Year	Event	Source
2001	FDA approval for acutely decompensated heart failure	IUPHAR record
2003	Reviews report haemodynamic and symptomatic improvement	Keating & Goa, Drugs 2003
2005	Meta-analyses raise renal-dysfunction and mortality concerns	Dorsch & Rodgers 2006; NEJM correspondence 2005
2011	Large outcomes trial; NEJM editorial: “the lost decade of nesiritide”	Topol, NEJM 2011

Registered studies today

ClinicalTrials.gov lists 286 registered studies mentioning nesiritide or its parent hormone as of September 2026, but most concern BNP and NT-proBNP as biomarkers — heart-failure screening in primary care, prognostic measurement before surgery — rather than the drug. One phase 4 trial of recombinant human BNP for prevention of acute kidney injury after cardiac surgery (NCT07617675) was listed as not yet recruiting, showing that the compound remains of interest in China, where recombinant BNP is marketed, even as its use in North America has faded.

Relation to other profiles

Nesiritide is the therapeutic copy of BNP, whose endogenous biology is profiled separately, and it sits alongside the CNP analogues vosoritide and navepegritide, which act on the sister receptor NPR-B to promote bone growth. It is an approved medicine administered intravenously in hospital; it is not a research peptide and does not appear in the grey market. This profile is educational and is not medical advice.

Structure & chemistry

Molecular identity & reference confidence

Source-supported reference

Reference values are taken from the cited molecular record or curated profile. A database match is not independent laboratory verification; modifications, counter-ions, and formulations can change the measured mass.

Molecular form: Recombinant human B-type natriuretic peptide, sequence identical to endogenous BNP; a ring-closed (disulfide-cyclised) peptide
Species: Not established by this molecular identity audit
Termini (N / C): Not specified / Not specified

Average reference mass

Reference policy updated: 2026-10-05

IUPHAR/BPS source snapshot · 2026-10-01
PubChem molecular record · 2026-10-01

Molecular formula: C143H244N50O42S4
Average reference mass: ≈ 3,464
Receptors: Natriuretic peptide receptor-A (NPR-A), a transmembrane guanylyl cyclase; signalling through intracellular cGMP
Backbone: Recombinant human B-type natriuretic peptide, sequence identical to endogenous BNP; a ring-closed (disulfide-cyclised) peptide
Status: Approved: FDA (2001) for acutely decompensated heart failure (IUPHAR record); clinical use declined after 2005–2011 safety and outcome data

Identifiers

PubChem CID: 71308561
IUPHAR ligand: 4890
ChEMBL: CHEMBL1201668
DrugBank: DB04899
CAS RN: 124584-08-3
UNII: P7WI8UL647

Chemistry values: curated profile, PubChem, IUPHAR/BPS Guide to Pharmacology · fetched 2026-10-01.

Clinical development snapshot

ClinicalTrials.gov lists 287 registered studies with “Nesiritide” as an intervention (snapshot 2026-10-01). A registry footprint is not evidence of efficacy or approval.

Registered studies

287

Highest phase reached

Phase 4

Active in latest 100

Most recent update

2026-09-29

Most recently updated studies
NCT	Title	Phase	Status	Updated
NCT07096726	Boston Medical Center Ultrasound Decongestion Study in Heart Failure	Not applicable	not yet recruiting	2026-09-29
NCT05791617	PET/MR in Post Stroke Cardiac Inflammation Study	—	terminated	2026-09-18
NCT07812207	Right Ventricular Afterload Indices in Lung Surgery	—	not yet recruiting	2026-09-10
NCT07765472	Subclinical Myocardial Dysfunction in Children With Wilson's Disease	—	active not recruiting	2026-08-14
NCT06183931	Study of ALXN2220 Versus Placebo in Adults With ATTR-CM	Phase 3	active not recruiting	2026-08-10
NCT07711821	PRIMARY-HF: Heart Failure Screening in Primary Care Using Point-of- Care	Not applicable	recruiting	2026-07-17

See all on ClinicalTrials.gov →

Concentration math

Nesiritide — reconstitution calculator

Enter how much peptide is in the vial and how much diluent (e.g. bacteriostatic water) is added. The tool returns the resulting solution concentration — and, for any amount you type, the volume it corresponds to. This is educational arithmetic, not a dosing recommendation.

Reference form: Recombinant human B-type natriuretic peptide, sequence identical to endogenous BNP; a ring-closed (disulfide-cyclised) peptideAverage reference mass: 3,464 Da

Peptide in vial (mg)

Diluent added (mL)

Syringe graduation

Solution concentration

5 mg/mL5,000 mcg/mL

Amount to measure (optional)

mcg

Enter an amount to see the volume it corresponds to.

Educational concentration mathematics only. This tool does not recommend a dose, amount, or protocol, and nothing here is medical advice. Many peptides are not authorized by Health Canada for human use — see our reconstitution and bacteriostatic-water guides for context.

Open the Nesiritide calculator on its own page →

Change log

Dated observations from the data pipeline (registry flags, trial footprints, identifiers) and editorial reviews of this profile.

2026-10-01Trials1 registered study added on ClinicalTrials.gov (now 287).
2026-09-08IdentifiersCross-linked to IUPHAR ligand 4890 and PubChem CID 71308561.
2026-09-08TrialsClinicalTrials.gov snapshot added: 286 registered studies, highest phase 4.
2026-09-08EditorialProfile content reviewed and updated by the editorial team.

FAQ about Nesiritide

What is Nesiritide?+

What Canadian product status is recorded for Nesiritide?+

Canadian product status for Nesiritide has not been verified in this profile. No verified record here does not mean no authorization exists. Status depends on the product, formulation and use; consult Health Canada's product records.

What is the typical length of Nesiritide?+

Nesiritide is not a classic amino-acid chain peptide in the same sense; see the profile for classification details.

What is nesiritide?+

The recombinant form of human B-type natriuretic peptide, sequence-identical to the hormone, approved by the FDA in 2001 as an intravenous vasodilator for acutely decompensated heart failure.

How does nesiritide work?+

It activates the guanylate cyclase receptor NPR-A in vascular smooth muscle and endothelium, raising cGMP, which dilates veins and arteries and enhances diuresis.

Is nesiritide still used?+

It remains approved, but use fell sharply after 2005 meta-analyses raised renal and mortality concerns and a large 2011 outcomes trial was neutral — the “lost decade of nesiritide”.

What is the difference between nesiritide and BNP?+

None chemically: nesiritide is recombinant BNP. BNP measured in blood tests (with NT-proBNP) is the same hormone used as a heart-failure biomarker.

Is nesiritide a research peptide?+

No. It is a hospital-administered approved medicine and is not sold in the research-peptide market.

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References & further reading

Disclaimer: Educational content only. Not medical advice. Not instructions for human use. Research peptides and unapproved products may be restricted or illegal to market for human consumption in your jurisdiction. Consult qualified professionals and applicable law.

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