Development of Natriuretic Peptide Receptor Agonists for Cardiovascular Diseases

Natriuretic peptide receptors (NPRs) play a crucial role in the development and progression of cardiovascular diseases. Modulating the activity of NPRs is a powerful strategy for preventing and treating cardiovascular diseases. As a leading contract research organization in cardiovascular disease research, Ace Therapeutics helps clients accelerate the discovery and development of NPR-A and NPR-B agonists

The Role of Natriuretic Peptide Receptor in Cardiovascular Diseases

The natriuretic peptide family includes atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), and C-type natriuretic peptide (CNP). NPR-A primarily binds ANP and BNP, activating guanylate cyclase and increasing intracellular cGMP levels, which mediate vasodilation, natriuresis, and diuresis. NPR-B binds CNP, activating guanylate cyclase and increasing cGMP levels to promote vasodilation and antiproliferative effects. Given their critical roles in cardiovascular regulation, NPR-A and NPR-B agonists represent a promising class of drugs for the treatment of cardiovascular diseases.

Fig. 1 Obesity and associated metabolic traits drive myocardial dysfunction and remodeling in obesity-HFPEF phenotype. (Egom EEA, 2021)

Discovery of Natriuretic Peptide Receptor Agonists

We provide R&D services for novel natriuretic peptide receptor agonists, including the development of long-acting monoclonal antibodies, novel small-molecule agonists, and recombinant peptides (peptide analogues). Concurrently, we can optimize delivery methods, progressing from intravenous infusion to subcutaneous injection and oral administration.

In Vitro Pharmacodynamic Studies

• Receptor Binding Assay
  We employ radioligand binding assays (RBA) to determine the affinity (Ki value) of drug candidates for NPRs, assessing their selectivity for different NPR subtypes (NPR-A, NPR-B and NPR-C).
• cGMP Assay
  We measure intracellular cGMP levels to evaluate the agonistic effects of drug candidates on NPRs, providing insights into their mechanisms of action and therapeutic potential.
• Calcium Ion Flow Measurements
  We utilize fluorescent dyes or electrophysiological techniques to assess the effects of drug candidates on calcium ion flow, offering a detailed understanding of their impact on cellular function.

In Vivo Pharmacodynamic Studies

• Effects on Hypertension
  We provide customized animal models of hypertension, such as the spontaneously hypertensive rat (SHR), to evaluate the antihypertensive effects of drugs. These models ensure robust preclinical efficacy, supporting the development of innovative therapies for hypertension.
• Effects on Heart Failure
  We offer different types of animal models of heart failure, including pressure overload-induced heart failure and myocardial ischemic heart failure models, to assess the effects of experimental drugs on cardiac function and remodeling.

Leveraging our dedicated research team and technology platform, Ace Therapeutics is committed to providing end-to-end preclinical research services for natriuretic peptide receptor agonist development. If you are interested in our services, please do not hesitate to contact us.

1. Egom, E.E.A. Natriuretic peptide clearance receptor (NPR-C) pathway as a novel therapeutic target in obesity-related heart failure with preserved ejection fraction (HFpEF). Front Physiol. 2021, 12:674254.