ArticleAmerican journal of physiology. Regulatory, integrative and comparative physiology2018
CRRL269: a novel designer and renal-enhancing pGC-A peptide activator.
Article in American journal of physiology. Regulatory, integrative and comparative physiology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
What it found
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Who cites it
18 citing papers in PubMed, 23 citations in OpenAlex.
- Beyond biomarkers: designer natriuretic peptides and cGMP centered therapies for cardiorenal and cardiometabolic protection in chronic heart failure.Internal and emergency medicine · 2026Review
- Natriuretic Peptides as Multisystem Regulators: From Clinical Biomarkers to Therapeutic Targets in Cardio-immunology.Cardiovascular drugs and therapy · 2026Review
- Novel enhancers of guanylyl cyclase-A activity acting via allosteric modulation.British journal of pharmacology · 2023Article
- Natriuretic Peptides: It Is Time for Guided Therapeutic Strategies Based on Their Molecular Mechanisms.International journal of molecular sciences · 2023Review
- Natriuretic peptide pathways in heart failure: further therapeutic possibilities.Cardiovascular research · 2023Article
- Natriuretic Peptide-Based Novel Therapeutics: Long Journeys of Drug Developments Optimized for Disease States.Biology · 2022Review
- MANP (M-Atrial Natriuretic Peptide) Reduces Blood Pressure and Furosemide-Induced Increase in Aldosterone in Hypertension.Hypertension (Dallas, Tex. : 1979) · 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
- First-in-Human Study of MANP: A Novel ANP (Atrial Natriuretic Peptide) Analog in Human Hypertension.Hypertension (Dallas, Tex. : 1979) · 2021Article
- 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
- Guanylyl Cyclase-cGMP Signaling Pathway in Melanocytes: Differential Effects of Altered Gravity in Non-Metastatic and Metastatic Cells.International journal of molecular sciences · 2020Review
- Novel Therapeutic Approaches Targeting the Renin-Angiotensin System and Associated Peptides in Hypertension and Heart Failure.Pharmacological reviews · 2019Review
- Emerging concepts of receptor endocytosis and concurrent intracellular signaling: Mechanisms of guanylyl cyclase/natriuretic peptide receptor-A activation and trafficking.Cellular signalling · 2019Review
- CRRL269.Circulation research · 2019Article
- I Kid(ney) You Not...Natriuretic Peptides Which Promote Natriuresis but Not Hypotension.Circulation research · 2019Article
- 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.Journal of molecular and cellular cardiology · 2019Article
- Protein Kinase G Is Involved in Acute but Not in Long-Term Regulation of Renin Secretion.Frontiers in pharmacology · 2019Article
- Particulate Guanylyl Cyclase A/cGMP Signaling Pathway in the Kidney: Physiologic and Therapeutic Indications.International journal of molecular sciences · 2018Review
Corrections and comments
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Authors and funding
11 authors at 2 institutions in 1 country.
Funding
Abstract
The natriuretic peptides (NPs) B-type NP (BNP) and urodilatin (URO) exert renal protective properties via the particulate guanylyl cyclase A receptor (pGC-A). As a potential renal-enhancing strategy, we engineered a novel designer peptide that we call CRRL269. CRRL269 was investigated in human cell lines and in normal canines to define potential cardiorenal enhancing actions. The mechanism of its cardiorenal selective properties was also investigated. In vitro NP receptor activity was quantified with guanosine 3',5'-cyclic monophosphate generation. In vivo effects were determined in normal canine acute infusion studies. We observed that CRRL269 demonstrated enhanced pGC-A activity in renal compared with nonrenal cell lines. CRRL269 exerted enhanced resistance to neprilysin compared with URO. Importantly, CRRL269 exhibited significant and greater increases in urinary sodium excretion and diuresis, with less blood pressure reduction, than BNP or URO in normal canines. CRRL269 retained potent renin-angiotensin-aldosterone system (RAAS) suppressing properties shared by URO and BNP. Also, CRRL269 exerted less arterial relaxation and higher cAMP cardiomyocytes generation than BNP. CRRL269 possessed superior renal and pGC-A activating properties compared with BNP or URO in vitro. CRRL269 exerted enhanced renal actions while suppressing RAAS in vivo and with less hypotension compared with URO or BNP. Together, our study suggests that CRRL269 is a promising innovative renal-enhancing drug, with favorable protective actions targeting cardiorenal disease states through the pGC-A receptor.
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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.