ArticleJournal of molecular and cellular cardiology2019
C53: A novel particulate guanylyl cyclase B receptor activator that has sustained activity in vivo with anti-fibrotic actions in human cardiac and renal fibroblasts.
Article in Journal of molecular and cellular cardiology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 30 citations in OpenAlex.
- Natriuretic Peptides as Multisystem Regulators: From Clinical Biomarkers to Therapeutic Targets in Cardio-immunology.Cardiovascular drugs and therapy · 2026Review
- Use of soluble guanylyl cyclase stimulators in heart failure therapy-a mode of action perspective.ESC heart failure · 2026Review
- Endothelial C-type natriuretic peptide/guanylyl cyclase-B signaling prevents pulmonary arterial hypertension.Nature communications · 2026Article
- Discovery of small molecule guanylyl cyclase B receptor positive allosteric modulators.PNAS nexus · 2024Article
- Emergent Peptides of the Antifibrotic Arsenal: Taking Aim at Myofibroblast Promoting Pathways.Biomolecules · 2023Review
- Evidence for Angiotensin II as a Naturally Existing Suppressor for the Guanylyl Cyclase A Receptor and Cyclic GMP Generation.International journal of molecular sciences · 2023Article
- Localization of natriuretic peptide receptors A, B, and C in healthy and diseased mouse kidneys.Pflugers Archiv : European journal of physiology · 2023Article
- CNP Promotes Antiarrhythmic Effects via Phosphodiesterase 2.Circulation research · 2023Article
- Natriuretic peptide pathways in heart failure: further therapeutic possibilities.Cardiovascular research · 2023Article
- Purification, characterization, and preliminary serial crystallography diffraction advances structure determination of full-length human particulate guanylyl cyclase A receptor.Scientific reports · 2022Article
- Discovery of small molecule guanylyl cyclase A receptor positive allosteric modulators.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- The CNP/NPR-B/cGMP Axis is a Therapeutic Target in Calcific Aortic Stenosis.JACC. Basic to translational science · 2021Article
- Prognostic Value of Urinary and Plasma C-Type Natriuretic Peptide in Acute Decompensated Heart Failure.JACC. Heart failure · 2021Article
- Novel therapeutics for the treatment of hypertension and its associated complications: peptide- and nonpeptide-based strategies.Hypertension research : official journal of the Japanese Society of Hypertension · 2021Review
- Natriuretic Peptides, Inflammation, and Sounding the Alarm.Circulation. Heart failure · 2020Article
- Cardiorenal syndrome: Multi-organ dysfunction involving the heart, kidney and vasculature.British journal of pharmacology · 2020Review
- Long-term blood pressure lowering and cGMP-activating actions of the novel ANP analog MANP.American journal of physiology. Regulatory, integrative and comparative physiology · 2020Article
- Discovery ofThe Journal of biological chemistry · 2019Article
- C-type Natriuretic Peptide: A Multifaceted Paracrine Regulator in the Heart and Vasculature.International journal of molecular sciences · 2019Review
Corrections and comments
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
Abstract
The native particulate guanylyl cyclase B receptor (pGC-B) activator, C-type natriuretic peptide (CNP), induces anti-remodeling actions in the heart and kidney through the generation of the second messenger 3', 5' cyclic guanosine monophosphate (cGMP). Indeed fibrotic remodeling, particularly in cardiorenal disease states, contributes to disease progression and thus, has been a key target for drug discovery and development. Although the pGC-B/cGMP system has been perceived as a promising anti-fibrotic pathway, its therapeutic potential is limited due to the rapid degradation and catabolism of CNP by neprilysin (NEP) and natriuretic peptide clearance receptor (NPRC). The goal of this study was to bioengineer and test in vitro and in vivo a novel pGC-B activator, C53. Here we established that C53 selectively generates cGMP via the pGC-B receptor and is highly resistant to NEP and has less interaction with NPRC in vitro. Furthermore in vivo, C53 had enhanced cGMP-generating actions that paralleled elevated plasma CNP-like levels, thus indicating a longer circulating half-life compared to CNP. Importantly in human cardiac fibroblasts (HCFs) and renal fibroblasts (HRFs), C53 exerted robust cGMP-generating actions, inhibited TGFβ-1 stimulated HCFs and HRFs proliferation chronically and suppressed the differentiation of HCFs and HRFs to myofibroblasts. The current findings advance innovation in drug discovery and highlight C53 as a novel pGC-B activator with sustained in vivo activity and anti-fibrotic actions in vitro. Future studies are warranted to explore the efficacy and therapeutic opportunity of C53 targeting fibrosis in cardiorenal disease states and beyond.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.