ArticleThe Journal of biological chemistry2015
Finerenone Impedes Aldosterone-dependent Nuclear Import of the Mineralocorticoid Receptor and Prevents Genomic Recruitment of Steroid Receptor Coactivator-1.
Article in The Journal of biological chemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 85 papers, 3 of them syntheses that pooled it.
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Who cites it
85 citing papers in PubMed, 3 syntheses or guidelines pooled it, 176 citations in OpenAlex.
- A systematic review and meta-analysis on the efficacy and safety of finerenone in the progression of heart failure.Frontiers in pharmacology · 2025Pooled it
- Efficacy and safety of nonsteroidal mineralocorticoid receptor antagonists for renal and cardiovascular outcomes in patients with chronic kidney disease: a meta-analysis of randomized clinical trials.Frontiers in pharmacology · 2024Pooled it
- Efficacy and safety of eplerenone treatment for patients with diabetic nephropathy: A meta-analysis.PloS one · 2022Pooled it
- Mineralocorticoid Receptor Antagonism with Finerenone: A New Era in the Management of Patients with Heart Failure with Mildly Reduced or Preserved Ejection Fraction.American journal of cardiovascular drugs : drugs, devices, and other interventions · 2025Trial
- Finerenone in Cardiorenal Disease: A Narrative Review of Molecular Mechanisms, Clinical Evidence, and Emerging Therapeutic Roles.Cardiovascular drugs and therapy · 2026Review
- In Silico Decoding of Nonsteroidal Mineralocorticoid Receptor Antagonist Binding: Implications for Drug Design.Journal of chemical information and modeling · 2026Article
- Impact of the Four Pillars on Electrolyte Derangements during State-of-the-Art Therapy for Diabetic Kidney Disease.Electrolyte & blood pressure : E & BP · 2026Review
- The Heart-Kidney Axis in Heart Failure and Chronic Kidney Disease: Mechanisms, Mediators, and Therapeutic Implications.Biomolecules · 2026Review
- Mineralocorticoid Receptor Antagonists for Liver Fibrosis: Potential Mechanisms and Research Progress.Journal of clinical and translational hepatology · 2026Review
- Finerenone mitigates acute alcoholic myocardial injury by modulating inflammatory signaling, oxidative stress, and mitochondrial function.Molecular medicine (Cambridge, Mass.) · 2026Article
- Intrarenal Hemodynamic Mechanisms of Kidney Protection by Nonsteroidal Mineralocorticoid Receptor Antagonists.Endocrinology and metabolism (Seoul, Korea) · 2026Review
- Nonsteroidal Mineralocorticoid Receptor Antagonists in Heart Failure: Mechanistic Basis, Clinical Evidence, and Therapeutic Integration.Drugs and drug candidates · 2026Article
- Mineralocorticoid receptor antagonists: Efficacy and safety in chronic kidney disease.Diabetes, obesity & metabolism · 2026Review
- Cardioprotective Effects of Finerenone Associated With the Suppression of Myocardial Sodium Accumulation in Aldosterone/Salt-Loaded Rats.Journal of the American Heart Association · 2026Article
- Kidney Effectiveness and Safety of Adding Spironolactone in Patients With Type 2 Diabetes Receiving Renin-Angiotensin System Inhibitors Therapy.Clinical and translational science · 2026Article
- Hemodynamic effects of finerenone on blood pressure and heart rate in hospitalized patients with type 2 diabetes: a real-world study.Frontiers in endocrinology · 2026Observational
- Non-albumin proteinuria as a candidate biomarker of treatment response to finerenone in diabetic kidney disease: a real-world cohort study.Frontiers in endocrinology · 2026Article
- Contemporary evidence of non-steroidal mineralocorticoid receptor antagonists in cardio-kidney-metabolic syndrome.Future cardiology · 2025Review
- Finerenone versus spironolactone in patients with chronic kidney disease and type 2 diabetes: a target trial emulation.Nature communications · 2025Article
- Regulation of Klotho Production by Mineralocorticoid Receptor Signaling in Renal Cell Lines.Biomolecules · 2025Article
25 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Aldosterone regulates sodium homeostasis by activating the mineralocorticoid receptor (MR), a member of the nuclear receptor superfamily. Hyperaldosteronism leads todeleterious effects on the kidney, blood vessels, and heart. Although steroidal antagonists such as spironolactone and eplerenone are clinically useful for the treatment of cardiovascular diseases, they are associated with several side effects. Finerenone, a novel nonsteroidal MR antagonist, is presently being evaluated in two clinical phase IIb trials. Here, we characterized the molecular mechanisms of action of finerenone and spironolactone at several key steps of the MR signaling pathway. Molecular modeling and mutagenesis approaches allowed identification of Ser-810 and Ala-773 as key residues for the high MR selectivity of finerenone. Moreover, we showed that, in contrast to spironolactone, which activates the S810L mutant MR responsible for a severe form of early onset hypertension, finerenone displays strict antagonistic properties. Aldosterone-dependent phosphorylation and degradation of MR are inhibited by both finerenone and spironolactone. However, automated quantification of MR subcellular distribution demonstrated that finerenone delays aldosterone-induced nuclear accumulation of MR more efficiently than spironolactone. Finally, chromatin immunoprecipitation assays revealed that, as opposed to spironolactone, finerenone inhibits MR, steroid receptor coactivator-1, and RNA polymerase II binding at the regulatory sequence of the SCNN1A gene and also remarkably reduces basal MR and steroid receptor coactivator-1 recruitment, unraveling a specific and unrecognized inactivating mechanism on MR signaling. Overall, our data demonstrate that the highly potent and selective MR antagonist finerenone specifically impairs several critical steps of the MR signaling pathway and therefore represents a promising new generation MR antagonist.
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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 OpenQuestion graph.