Year: 2026
Type: conference-paper
Abstract: The public health burden related to the morbidity and mortality of hypertension is enormous and increasing. In 2023, WHO reported that 1.3 billion patients worldwide are diagnosed with hypertension (HT), from which 10‐15% suffer from resistant HT (RHT). RHT is a frequent disease, and its prevalence continues to rise, additionally it causes premature morbidity and death, since currently there are limited therapeutic options. Thus, the development of novel drugs that can control the elevated blood pressure in these patients is urgent and of high social and clinical impact for several millions of people worldwide. Natriuretic peptides are important in the regulation of blood pressure. Activation of natriuretic peptide receptor A (NPR-A; GC-A) by endogenous atrial natriuretic peptide (ANP) and B-type natriuretic peptide (BNP) via production of cyclic guanosine monophosphate (cGMP) is associated with several beneficial cardiovascular and renal effects. Our novel approach is to find a small molecule to treat RHT, through a novel mechanism of action, targeting NPR-A. Through several rounds of screening, we have found small molecular allosteric modulators which increase the efficacy and potency of BNP and ANP in their ability to activate NPR‐A and generate cGMP. These compounds were characterized as NPR-A-selective allosteric enhancers, and their activity is dependent on one unique amino acid in NPR-A. Finally, in an animal model, we have also obtained preliminary evidence for their efficacy in vivo.
Language: English
Subfield: Cardiology and Cardiovascular Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: gold
OpenAlex ID: W7163167567