ArticlePloS one2015
Discovery and cardioprotective effects of the first non-Peptide agonists of the G protein-coupled prokineticin receptor-1.
Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 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
28 citing papers in PubMed, 63 citations in OpenAlex.
- Celecoxib Enhances Oxidative Muscle Fibre Formation and Improves Muscle Functions Through Prokr1 Activation in Mice.Journal of cachexia, sarcopenia and muscle · 2025Article
- Genetic Polymorphisms of Prokineticins and Prokineticin Receptors Associated with Human Disease.Life (Basel, Switzerland) · 2024Review
- Therapeutic Potential of Targeting Prokineticin Receptors in Diseases.Pharmacological reviews · 2023Review
- Non-Peptide Agonists and Antagonists of the Prokineticin Receptors.Current issues in molecular biology · 2022Review
- Identification of Regions Involved in the Physical Interaction between Melanocortin Receptor Accessory Protein 2 and Prokineticin Receptor 2.Biomolecules · 2022Article
- Identification and Characterization of a New Splicing Variant of Prokineticin 2.Life (Basel, Switzerland) · 2022Article
- Prokineticin-Receptor Network: Mechanisms of Regulation.Life (Basel, Switzerland) · 2022Review
- Recapturing embryonic potential in the adult epicardium: Prospects for cardiac repair.Stem cells translational medicine · 2021Review
- Prokineticin receptor 1 ameliorates insulin resistance in skeletal muscle.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2021Article
- Structure-activity relationships study of isothiocyanates for HJournal of advanced research · 2021Review
- Trehalose Ameliorates Diabetic Cardiomyopathy: Role of the PK2/PKR Pathway.Oxidative medicine and cellular longevity · 2021Article
- Updates on Anticancer Therapy-Mediated Vascular Toxicity and New Horizons in Therapeutic Strategies.Frontiers in cardiovascular medicine · 2021Review
- The Role of Prokineticin 2 in Oxidative Stress and in Neuropathological Processes.Frontiers in pharmacology · 2021Review
- Cinnamides TargetMolecules (Basel, Switzerland) · 2020Article
- Prokineticin signaling in heart-brain developmental axis: Therapeutic options for heart and brain injuries.Pharmacological research · 2020Review
- Roles of Prokineticin 2 in Subarachnoid Hemorrhage-Induced Early Brain Injury via Regulation of Phenotype Polarization in Astrocytes.Molecular neurobiology · 2020Article
- Metformin Ameliorates Diabetic Cardiomyopathy by Activating the PK2/PKR Pathway.Frontiers in physiology · 2020Article
- The Citrus Flavonoid Naringenin Protects the Myocardium from Ageing-Dependent Dysfunction: Potential Role of SIRT1.Oxidative medicine and cellular longevity · 2020Article
- Prokineticin-izing Doxorubicin-Damaged Hearts.JACC. CardioOncology · 2019Article
- Prokineticin Receptor-1 Signaling Inhibits Dose- and Time-Dependent Anthracycline-Induced Cardiovascular Toxicity Via Myocardial and Vascular Protection.JACC. CardioOncology · 2019Article
Corrections and comments
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Authors and funding
9 authors at 6 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Prokineticins are angiogenic hormones that activate two G protein-coupled receptors: PKR1 and PKR2. PKR1 has emerged as a critical mediator of cardiovascular homeostasis and cardioprotection. Identification of non-peptide PKR1 agonists that contribute to myocardial repair and collateral vessel growth hold promises for treatment of heart diseases. Through a combination of in silico studies, medicinal chemistry, and pharmacological profiling approaches, we designed, synthesized, and characterized the first PKR1 agonists, demonstrating their cardioprotective activity against myocardial infarction (MI) in mice. Based on high throughput docking protocol, 250,000 compounds were computationally screened for putative PKR1 agonistic activity, using a homology model, and 10 virtual hits were pharmacologically evaluated. One hit internalizes PKR1, increases calcium release and activates ERK and Akt kinases. Among the 30 derivatives of the hit compound, the most potent derivative, IS20, was confirmed for its selectivity and specificity through genetic gain- and loss-of-function of PKR1. Importantly, IS20 prevented cardiac lesion formation and improved cardiac function after MI in mice, promoting proliferation of cardiac progenitor cells and neovasculogenesis. The preclinical investigation of the first PKR1 agonists provides a novel approach to promote cardiac neovasculogenesis after MI.
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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.