ArticleJournal of medicinal chemistry2017
Structure-Based Design of Highly Selective and Potent G Protein-Coupled Receptor Kinase 2 Inhibitors Based on Paroxetine.
Erratum issuedOpen access · greenAbstract read
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Article in Journal of medicinal chemistry, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 31 papers.
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31citing papers in PubMed
2.7field-weighted citation impact, top 9% of its field
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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.
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Who cites it
31 citing papers in PubMed, 55 citations in OpenAlex.
- Recent advances in the development of GRK2 inhibitors: blocking the interaction of GRK2 with its partners.Acta pharmacologica Sinica · 2026Review
- Beyond β-Adrenergic Receptor Brake: Compartment-Selective GRK2 Programs from Heart Failure to Cardio-Oncology.Kinases and phosphatases · 2026Article
- Cell-based and isoform-selective G protein-coupled receptor kinase assays for comprehensive inhibitor evaluation.Communications biology · 2026Article
- Novel role of GRK2 in isoprenaline-induced activation of NaMolecular biology reports · 2025Article
- A New GRK2 Inhibitor for Heart Failure.JACC. Basic to translational science · 2025Article
- Therapeutic Efficacy of a Novel Pharmacologic GRK2 Inhibitor in Multiple Animal Models of Heart Failure.JACC. Basic to translational science · 2025Article
- Design, synthesis, and X-ray structural studies of a series of highly potent, selective, and drug-like G protein-coupled receptor kinase 5 inhibitors.European journal of medicinal chemistry · 2025Article
- A simple and scalable zebrafish model of Sonic hedgehog medulloblastoma.Cell reports · 2024Article
- GRK2 kinases in the primary cilium initiate SMOOTHENED-PKA signaling in the Hedgehog cascade.PLoS biology · 2024Article
- InfluenZing Lung Fibrosis: Reinforcing Endothelial Surface Expression of S1PR1 to Attenuate Post-Acute Respiratory Distress Syndrome Lung Remodeling.American journal of respiratory cell and molecular biology · 2024Article
- Cardioprotective Effects of the GRK2 Inhibitor Paroxetine on Isoproterenol-Induced Cardiac Remodeling by Modulating NF-κB Mediated Prohypertrophic and Profibrotic Gene Expression.International journal of molecular sciences · 2023Article
- Control of GαScience advances · 2022Article
- A bead-based GPCR phosphorylation immunoassay for high-throughput ligand profiling and GRK inhibitor screening.Communications biology · 2022Article
- Sex/Gender- and Age-Related Differences in β-Adrenergic Receptor Signaling in Cardiovascular Diseases.Journal of clinical medicine · 2022Review
- Targeted inhibition of GRK2 kinase domain by CP-25 to reverse fibroblast-like synoviocytes dysfunction and improve collagen-induced arthritis in rats.Acta pharmaceutica Sinica. B · 2021Article
- Nuisance compounds in cellular assays.Cell chemical biology · 2021Review
- Paroxetine-Overview of the Molecular Mechanisms of Action.International journal of molecular sciences · 2021Review
- Targeting G protein-coupled receptor kinases (GRKs) to G protein-coupled receptors.Current opinion in endocrine and metabolic research · 2021Article
- Generation of Highly Selective, Potent, and Covalent G Protein-Coupled Receptor Kinase 5 Inhibitors.Journal of medicinal chemistry · 2021Article
- Case Report: A NovelFrontiers in neurology · 2021Article
Corrections and comments
- Erratum issued
Authors and funding
11 authors at 1 institution in 1 country.
Helen V WaldschmidtDepartment of Medicinal Chemistry, College of Pharmacy, ‡Departments of Pharmacology and Biological Chemistry, Life Sciences Institute, §Ph.D. Program in Chemical Biology, ⊥Vahlteich Medicinal Chemistry Core, University of Michigan , Ann Arbor, Michigan 48109, United States.
Kristoff T HomanDepartment of Medicinal Chemistry, College of Pharmacy, ‡Departments of Pharmacology and Biological Chemistry, Life Sciences Institute, §Ph.D. Program in Chemical Biology, ⊥Vahlteich Medicinal Chemistry Core, University of Michigan , Ann Arbor, Michigan 48109, United States.
Marilyn C CatoDepartment of Medicinal Chemistry, College of Pharmacy, ‡Departments of Pharmacology and Biological Chemistry, Life Sciences Institute, §Ph.D. Program in Chemical Biology, ⊥Vahlteich Medicinal Chemistry Core, University of Michigan , Ann Arbor, Michigan 48109, United States.
Osvaldo Cruz-RodríguezDepartment of Medicinal Chemistry, College of Pharmacy, ‡Departments of Pharmacology and Biological Chemistry, Life Sciences Institute, §Ph.D. Program in Chemical Biology, ⊥Vahlteich Medicinal Chemistry Core, University of Michigan , Ann Arbor, Michigan 48109, United States.
Alessandro CannavoDepartment of Medicinal Chemistry, College of Pharmacy, ‡Departments of Pharmacology and Biological Chemistry, Life Sciences Institute, §Ph.D. Program in Chemical Biology, ⊥Vahlteich Medicinal Chemistry Core, University of Michigan , Ann Arbor, Michigan 48109, United States.
Michael W WilsonDepartment of Medicinal Chemistry, College of Pharmacy, ‡Departments of Pharmacology and Biological Chemistry, Life Sciences Institute, §Ph.D. Program in Chemical Biology, ⊥Vahlteich Medicinal Chemistry Core, University of Michigan , Ann Arbor, Michigan 48109, United States.
Jianliang SongDepartment of Medicinal Chemistry, College of Pharmacy, ‡Departments of Pharmacology and Biological Chemistry, Life Sciences Institute, §Ph.D. Program in Chemical Biology, ⊥Vahlteich Medicinal Chemistry Core, University of Michigan , Ann Arbor, Michigan 48109, United States.
Joseph Y CheungDepartment of Medicinal Chemistry, College of Pharmacy, ‡Departments of Pharmacology and Biological Chemistry, Life Sciences Institute, §Ph.D. Program in Chemical Biology, ⊥Vahlteich Medicinal Chemistry Core, University of Michigan , Ann Arbor, Michigan 48109, United States.
Walter J KochDepartment of Medicinal Chemistry, College of Pharmacy, ‡Departments of Pharmacology and Biological Chemistry, Life Sciences Institute, §Ph.D. Program in Chemical Biology, ⊥Vahlteich Medicinal Chemistry Core, University of Michigan , Ann Arbor, Michigan 48109, United States.
John J G TesmerDepartment of Medicinal Chemistry, College of Pharmacy, ‡Departments of Pharmacology and Biological Chemistry, Life Sciences Institute, §Ph.D. Program in Chemical Biology, ⊥Vahlteich Medicinal Chemistry Core, University of Michigan , Ann Arbor, Michigan 48109, United States.
Scott D LarsenDepartment of Medicinal Chemistry, College of Pharmacy, ‡Departments of Pharmacology and Biological Chemistry, Life Sciences Institute, §Ph.D. Program in Chemical Biology, ⊥Vahlteich Medicinal Chemistry Core, University of Michigan , Ann Arbor, Michigan 48109, United States.ORCID 0000-0001-8440-4990
University of Michigan · US
Funding
Regulation of Beta-Adrenergic Receptor Signaling by S-NitrosylationP01HL075443 · NHLBI · DUKE UNIVERSITY · PI XIAO, KUNHONG · 2004 to 2019
$26.1MTargeted Cancer Therapeutics and Heart Failure: Mechanisms and Post-injury RepairP01HL091799 · NHLBI · THOMAS JEFFERSON UNIVERSITY · PI KOCH, WALTER J. · 2008 to 2018
$23.1MPKC alpha as a translational target in Heart FailureP01HL108806 · NHLBI · TEMPLE UNIV OF THE COMMONWEALTH · PI RABINOWITZ, JOSEPH E · 2012 to 2016
$11.3MStructure, function, and inhibition of G protein-coupled receptor kinasesR01HL071818 · NHLBI · UNIVERSITY OF TEXAS AUSTIN · PI TESMER, JOHN · 2004 to 2023
$7.1MMICHIGAN CHEMISTRY-BIOLOGY INTERFACE TRAINING PROGRAMT32GM008597 · NIGMS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI MONTGOMERY, JOHN · 1996 to 2018
$5.0MTargeting GRK2 in the HeartR01HL061690 · NHLBI · THOMAS JEFFERSON UNIVERSITY · PI KOCH, WALTER J. · 1998 to 2022
$4.2MTargeting GRK2 (BARK1) in Heart FailureR37HL061690 · NHLBI · THOMAS JEFFERSON UNIVERSITY · PI KOCH, WALTER J. · 2009 to 2018
$3.9MStructural Studies of Galphaq and Its Complexes at the Cell MembraneR01HL086865 · NHLBI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI TESMER, JOHN · 2007 to 2015
$3.0MStructure and Function of the LPLA2/LCAT Acyltransferase FamilyR01HL122416 · NHLBI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI TESMER, JOHN · 2015 to 2018
$1.9MNHLBI NIH HHS P01 HL075443NHLBI NIH HHS P01 HL091799NHLBI NIH HHS P01 HL108806NHLBI NIH HHS R01 HL061690NHLBI NIH HHS R01 HL071818NHLBI NIH HHS R01 HL086865NHLBI NIH HHS R01 HL122416NHLBI NIH HHS R37 HL061690NIGMS NIH HHS T32 GM008597
Abstract
In heart failure, the β-adrenergic receptors (βARs) become desensitized and uncoupled from heterotrimeric G proteins. This process is initiated by G protein-coupled receptor kinases (GRKs), some of which are upregulated in the failing heart, making them desirable therapeutic targets. The selective serotonin reuptake inhibitor, paroxetine, was previously identified as a GRK2 inhibitor. Utilizing a structure-based drug design approach, we modified paroxetine to generate a small compound library. Included in this series is a highly potent and selective GRK2 inhibitor, 14as, with an IC
Indexed as
Drug DesignAnimalsCrystallography, X-RayG-Protein-Coupled Receptor Kinase 2HumansMiceMicrosomes, LiverMolecular Docking SimulationParoxetineProtein Kinase InhibitorsG-Protein-Coupled Receptor Kinase 2ParoxetineProtein Kinase Inhibitors
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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 Socratic graph.