ArticleJCI insight2020
Cardiovascular response to small-molecule APJ activation.
Article in JCI insight, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
24 citing papers in PubMed, 44 citations in OpenAlex.
- A First-in-Human Study of AMG 986, a Novel Apelin Receptor Agonist, in Healthy Subjects and Heart Failure Patients.Cardiovascular drugs and therapy · 2023Trial
- Evaluation of the Pharmacokinetics and Safety of AMG 986 Tablet and Capsule Formulations in Healthy Adult Subjects: A Phase I, Open-Label, Randomized Study.Drugs in R&D · 2022Trial
- The Apelin-APJ Axis in Heart Failure: Mechanistic Insights, Clinical Evidence, and Translational Challenges.Cardiovascular drugs and therapy · 2026Review
- Apelin-APLNR pathway across development, inflammation, and vascular remodeling: an endothelial perspective.Experimental & molecular medicine · 2026Review
- International Union of Basic and Clinical Pharmacology. CXXI. Apelin receptor pharmacology in the human cardiovascular system and emerging clinical applications.Pharmacological reviews · 2026Review
- Dynamic monomer-dimer transition in ligand-induced apelin receptor activation.Nature communications · 2026Article
- Review
- The Apelinergic System in Kidney Disease: Novel Perspectives.International journal of molecular sciences · 2025Review
- The Impact of the Apelinergic System on the Cardiovascular System.International journal of molecular sciences · 2025Review
- Metabolically stable apelin analogs: development and functional role in water balance and cardiovascular function.Clinical science (London, England : 1979) · 2025Review
- Structural and functional determination of peptide versus small molecule ligand binding at the apelin receptor.Nature communications · 2024Article
- Skeletal Muscle Injury in Chronic Kidney Disease-From Histologic Changes to Molecular Mechanisms and to Novel Therapies.International journal of molecular sciences · 2024Review
- The Apelin/APJ System: A Potential Therapeutic Target for Sepsis.Journal of inflammation research · 2024Review
- Design and preclinical evaluation of a novel apelin-based PET radiotracer targeting APJ receptor for molecular imaging of angiogenesis.Angiogenesis · 2023Article
- Signaling Modulation via Minimal C-Terminal Modifications of Apelin-13.ACS pharmacology & translational science · 2023Article
- The G protein-coupled receptor ligand apelin-13 ameliorates skeletal muscle atrophy induced by chronic kidney disease.Journal of cachexia, sarcopenia and muscle · 2023Article
- Ventriculo-arterial (un)coupling in septic shock: Impact of current and upcoming hemodynamic drugs.Frontiers in cardiovascular medicine · 2023Review
- Apelin alleviated neuroinflammation and promoted endogenous neural stem cell proliferation and differentiation after spinal cord injury in rats.Journal of neuroinflammation · 2022Article
- A Phase I, Open-label, Single-Dose Study to Evaluate the Pharmacokinetics, Safety, and Tolerability of AMG 986 in Healthy Japanese Subjects.Drugs in R&D · 2022Article
- The microRNA-204-5p inhibits APJ signalling and confers resistance to cardiac hypertrophy and dysfunction.Clinical and translational medicine · 2022Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
34 authors at 1 institution in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Heart failure (HF) remains a grievous illness with poor prognosis even with optimal care. The apelin receptor (APJ) counteracts the pressor effect of angiotensin II, attenuates ischemic injury, and has the potential to be a novel target to treat HF. Intravenous administration of apelin improves cardiac function acutely in patients with HF. However, its short half-life restricts its use to infusion therapy. To identify a longer acting APJ agonist, we conducted a medicinal chemistry campaign, leading to the discovery of potent small-molecule APJ agonists with comparable activity to apelin by mimicking the C-terminal portion of apelin-13. Acute infusion increased systolic function and reduced systemic vascular resistance in 2 rat models of impaired cardiac function. Similar results were obtained in an anesthetized but not a conscious canine HF model. Chronic oral dosing in a rat myocardial infarction model reduced myocardial collagen content and improved diastolic function to a similar extent as losartan, a RAS antagonist standard-of-care therapy, but lacked additivity with coadministration. Collectively, this work demonstrates the feasibility of developing clinical, viable, potent small-molecule agonists that mimic the endogenous APJ ligand with more favorable drug-like properties and highlights potential limitations for APJ agonism for this indication.
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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.