ArticleMolecules (Basel, Switzerland)2014
Identification and characterization of amlexanox as a G protein-coupled receptor kinase 5 inhibitor.
Article in Molecules (Basel, Switzerland), 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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
31 citing papers in PubMed, 53 citations in OpenAlex.
- TANK-binding kinase 1 protects against MASH progression via mitochondrial quality control.Experimental & molecular medicine · 2026Article
- Pharmacological inhibition of G protein-coupled receptor kinase 5 decreases high-fat diet-induced hepatic steatosis in mice.Biochemical and biophysical research communications · 2026Article
- Potential Cardioprotective Effect of a GRK5 Inhibitor Against NF-κB-Mediated Inflammation in an Animal Model of Isoproterenol-Induced Myocardial Infarction.International journal of molecular sciences · 2025Article
- Tank-Binding Kinase 1 protects against MASH progression via mitochondrial quality control.Research square · 2025Article
- Type 2 diabetes susceptibility gene GRK5 regulates physiological pancreatic β-cell proliferation via phosphorylation of HDAC5.iScience · 2023Article
- Novel roles for G protein-coupled receptor kinases in cardiac injury and repair.Biochemical Society transactions · 2023Review
- Sex/Gender- and Age-Related Differences in β-Adrenergic Receptor Signaling in Cardiovascular Diseases.Journal of clinical medicine · 2022Review
- Genetic Catalytic Inactivation of GRK5 Impairs Cardiac Function in Mice Via Dysregulated P53 Levels.JACC. Basic to translational science · 2022Article
- G protein-coupled receptor kinase 5 deletion suppresses synovial inflammation in a murine model of collagen antibody-induced arthritis.Scientific reports · 2021Article
- Targeting GRK5 for Treating Chronic Degenerative Diseases.International journal of molecular sciences · 2021Review
- Review
- Amlexanox and Forskolin Prevents Isoproterenol-Induced Cardiomyopathy by Subduing Cardiomyocyte Hypertrophy and Maladaptive Inflammatory Responses.Frontiers in cell and developmental biology · 2021Article
- Isoproterenol-Induced Cardiomyopathy Recovery Intervention: Amlexanox and Forskolin Enhances the Resolution of Catecholamine Stress-Induced Maladaptive Myocardial Remodeling.Frontiers in cardiovascular medicine · 2021Article
- KR-39038, a Novel GRK5 Inhibitor, Attenuates Cardiac Hypertrophy and Improves Cardiac Function in Heart Failure.Biomolecules & therapeutics · 2020Article
- Characterization of GRK5 as a novel regulator of rhabdomyosarcoma tumor cell growth and self-renewal.Oncotarget · 2020Article
- G protein-coupled receptor kinases as therapeutic targets in the heart.Nature reviews. Cardiology · 2019Review
- Fluorescence-based investigations of RNA-small molecule interactions.Methods (San Diego, Calif.) · 2019Article
- Nuclear translocation of calmodulin in pathological cardiac hypertrophy originates from ryanodine receptor bound calmodulin.Journal of molecular and cellular cardiology · 2018Article
- Carboxylic Acid Derivatives of Amlexanox Display Enhanced Potency toward TBK1 and IKKMolecular pharmacology · 2018Article
- Chronic ethanol consumption: role of TLR3/TRIF-dependent signaling.Addiction biology · 2018Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
G protein-coupled receptor kinases (GRKs) have been implicated in human diseases ranging from heart failure to diabetes. Previous studies have identified several compounds that selectively inhibit GRK2, such as paroxetine and balanol. Far fewer selective inhibitors have been reported for GRK5, a target for the treatment of cardiac hypertrophy, and the mechanism of action of reported compounds is unknown. To identify novel scaffolds that selectively inhibit GRK5, a differential scanning fluorometry screen was used to probe a library of 4480 compounds. The best hit was amlexanox, an FDA-approved anti-inflammatory, anti-allergic immunomodulator. The crystal structure of amlexanox in complex with GRK1 demonstrates that its tricyclic aromatic ring system forms ATP-like interactions with the hinge of the kinase domain, which is likely similar to how this drug binds to IκB kinase ε (IKKε), another kinase known to be inhibited by this compound. Amlexanox was also able to inhibit myocyte enhancer factor 2 transcriptional activity in neonatal rat ventricular myocytes in a manner consistent with GRK5 inhibition. The GRK1 amlexanox structure thus serves as a springboard for the rational design of inhibitors with improved potency and selectivity for GRK5 and IKKε.
Indexed as
Identifiers
What OpenQuestion holds
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.