ArticleFrontiers in pharmacology2018
Digoxin, an Overlooked Agonist of RORγ/RORγT.
Article in Frontiers in pharmacology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 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
17 citing papers in PubMed, 29 citations in OpenAlex.
- NaFrontiers in chemistry · 2026Article
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- Cardiac Glycosides: From Natural Defense Molecules to Emerging Therapeutic Agents.Biomolecules · 2025Review
- Evaluation of the Anti-Mycobacterial and Anti-Inflammatory Activities of the New Cardiotonic Steroid γ-Benzylidene Digoxin-15 in Macrophage Models of Infection.Microorganisms · 2025Article
- Digoxin and its NaBioorganic & medicinal chemistry · 2024Review
- Simultaneous Increases in Intracellular Sodium and Tonicity Boost Antimicrobial Activity of Macrophages.Cells · 2023Article
- International Union of Basic and Clinical Pharmacology CXIII: Nuclear Receptor Superfamily-Update 2023.Pharmacological reviews · 2023Review
- New uses for an old remedy: Digoxin as a potential treatment for steatohepatitis and other disorders.World journal of gastroenterology · 2023Review
- Revitalizing myocarditis treatment through gut microbiota modulation: unveiling a promising therapeutic avenue.Frontiers in cellular and infection microbiology · 2023Review
- Timed use of digoxin prevents heart ischemia-reperfusion injury through a REV-ERBα-UPS signaling pathway.Nature cardiovascular research · 2022Article
- Identification of Corosolic and Oleanolic Acids as Molecules Antagonizing the Human RORγT Nuclear Receptor Using the Calculated Fingerprints of the Molecular Similarity.International journal of molecular sciences · 2022Article
- ROR: Nuclear Receptor for Melatonin or Not?Molecules (Basel, Switzerland) · 2021Review
- Cardiac Glycosides as Immune System Modulators.Biomolecules · 2021Review
- Article
- (Inverse) Agonists of Retinoic Acid-Related Orphan Receptor γ: Regulation of Immune Responses, Inflammation, and Autoimmune Disease.Annual review of pharmacology and toxicology · 2020Review
- The Dichotomous Nature of AZ5104 (an EGFR Inhibitor) Towards RORγ and RORγT.International journal of molecular sciences · 2019Article
- SIRT2 Contributes to the Resistance of Melanoma Cells to the Multikinase Inhibitor Dasatinib.Cancers · 2019Article
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Digoxin was one of the first identified RORγT receptor inverse agonists inhibiting the differentiation of Th17 cells. However, this compound exhibits inhibitory activity at relatively high concentrations that mediate cytotoxic effects. We previously identified several cardenolides that are structurally similar to digoxin that were able to induce RORγ/RORγT-dependent transcription. These observations encouraged us to reanalyze the effects of digoxin on RORγ/RORγT-dependent transcription at low, noncytotoxic concentrations. Digoxin induced RORγ/RORγT-dependent transcription in HepG2 and Th17 cells. Furthermore, analysis of the transcriptomes of Th17 cells cultured in the presence of digoxin revealed the induction of the expression of numerous Th17-specific genes, including IL17A/F, IL21, IL22, IL23R, CCR4, and CCR6. Thus, our study, which includes data obtained from intact cells, indicates that digoxin, similar to other cardenolides, is a potent RORγ/RORγT receptor activator and that its structure may serve as a starting point for the design of dedicated molecules that can be used in the development of adoptive cell therapy (ACT).
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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.