ArticleACS chemical biology2012
Paroxetine is a direct inhibitor of g protein-coupled receptor kinase 2 and increases myocardial contractility.
Article in ACS chemical biology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 122 papers.
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The trial behind it
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Who cites it
122 citing papers in PubMed, 202 citations in OpenAlex.
- Efficacy of Paroxetine as an Adjuvant Therapy in Rheumatoid Arthritis Patients: A Randomized Controlled Study.Drug design, development and therapy · 2025Trial
- The impact of paroxetine on insulin secretion and sensitivity through AKT/GLUT4 axis.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- Recent advances in the development of GRK2 inhibitors: blocking the interaction of GRK2 with its partners.Acta pharmacologica Sinica · 2026Review
- EphB1 Receptor Blockade Augments Morphine Antinociception via Inhibiting GRK2-Mediated µ-Opioid Receptor Internalization.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Beyond β-Adrenergic Receptor Brake: Compartment-Selective GRK2 Programs from Heart Failure to Cardio-Oncology.Kinases and phosphatases · 2026Article
- Pharmacological inhibition of G protein-coupled receptor kinase 2 (GRK2) by paroxetine attenuates acetaminophen-induced hepatotoxicity.The Korean journal of physiology & pharmacology : official journal of the Korean Physiological Society and the Korean Society of Pharmacology · 2026Article
- Analysis of GRK2 aggregation in the pathology of Alzheimer disease in animal models.Cell reports. Medicine · 2026Article
- Repurposing the SSRI paroxetine increases lymphocyte mobilization and improves the efficacy of measles virus-based immunovirotherapy.Molecular therapy. Oncology · 2026Article
- Evaluating the Antiviral Efficacy of Encapsulated PKC Inhibitor BIM-I against influenza A Virus Infection.Advanced healthcare materials · 2026Article
- Cell-based and isoform-selective G protein-coupled receptor kinase assays for comprehensive inhibitor evaluation.Communications biology · 2026Article
- miR-181a post-transcriptionally targets GRK2 to limit maladaptive signaling in cardiomyocytes.Frontiers in cardiovascular medicine · 2026Article
- Drug Repositioning in Doxorubicin-Induced Cardiotoxicity Protection.International journal of molecular sciences · 2025Review
- Exploiting host kinases to combat dengue virus infection and disease.Antiviral research · 2025Review
- FGFR2 residence in primary cilia is necessary for epithelial cell signaling.The Journal of cell biology · 2025Article
- Logic-based machine learning predicts how escitalopram attenuates cardiomyocyte hypertrophy.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Paroxetine alleviates dendritic cell and T lymphocyte activation via GRK2-mediated PI3K-AKT signaling in rheumatoid arthritis.Chinese medical journal · 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
- Unveiling the Role of GRK2: From Immune Regulation to Cancer Therapeutics.Mediators of inflammation · 2025Review
- Potential cardioprotective effect of paroxetine against ventricular remodeling in an animal model of myocardial infarction: a comparative study.BMC pharmacology & toxicology · 2024Article
62 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
13 authors at 4 institutions in 1 country.
Funding
Abstract
G protein-coupled receptor kinase 2 (GRK2) is a well-established therapeutic target for the treatment of heart failure. Herein we identify the selective serotonin reuptake inhibitor (SSRI) paroxetine as a selective inhibitor of GRK2 activity both in vitro and in living cells. In the crystal structure of the GRK2·paroxetine-Gβγ complex, paroxetine binds in the active site of GRK2 and stabilizes the kinase domain in a novel conformation in which a unique regulatory loop forms part of the ligand binding site. Isolated cardiomyocytes show increased isoproterenol-induced shortening and contraction amplitude in the presence of paroxetine, and pretreatment of mice with paroxetine before isoproterenol significantly increases left ventricular inotropic reserve in vivo with no significant effect on heart rate. Neither is observed in the presence of the SSRI fluoxetine. Our structural and functional results validate a widely available drug as a selective chemical probe for GRK2 and represent a starting point for the rational design of more potent and specific GRK2 inhibitors.
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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.