ArticleThe Journal of clinical investigation2017
Macrolides selectively inhibit mutant KCNJ5 potassium channels that cause aldosterone-producing adenoma.
Article in The Journal of clinical investigation, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03414918 (Macrolides for KCNJ5 - Mutated Aldosterone-Producing Adenoma), which is not on this map. Cited by 34 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.
Macrolides for KCNJ5 - Mutated Aldosterone-Producing Adenoma (MAPA): A Study Of Personalized Diagnosis of Primary Aldosteronism With Implications For Treatment
Who cites it
34 citing papers in PubMed, 71 citations in OpenAlex.
- Inter- and intratumoral heterogeneity of aldosterone-producing adenomas: recent advances and clinical implications.Endocrine journal · 2026Review
- Antibiotics and the Endocrine System: Mechanisms, Adverse Effects, and Clinical Implications.Antibiotics (Basel, Switzerland) · 2026Review
- Primary aldosteronism.Nature reviews. Disease primers · 2026Review
- Review
- An In Silico Investigation of the Pathogenic G151R G Protein-Gated Inwardly Rectifying KBiology · 2024Article
- Double CYP11B1/CYP11B2 Immunohistochemistry and Detection of KCNJ5 Mutations in Primary Aldosteronism.The Journal of clinical endocrinology and metabolism · 2024Article
- Treating Primary Aldosteronism-Induced Hypertension: Novel Approaches and Future Outlooks.Endocrine reviews · 2024Article
- Identification of Potential Modulators of a Pathogenic G Protein-Gated Inwardly Rectifying KMolecules (Basel, Switzerland) · 2023Article
- Primary aldosteronism: molecular medicine meets public health.Nature reviews. Nephrology · 2023Review
- Cardiovascular and metabolic characters ofFrontiers in endocrinology · 2023Review
- YM750, an ACAT Inhibitor, Acts on Adrenocortical Cells to Inhibit Aldosterone Secretion Due to Depolarization.International journal of molecular sciences · 2022Article
- Clinical Translationality ofInternational journal of molecular sciences · 2022Review
- Genetics of Primary Aldosteronism.Hypertension (Dallas, Tex. : 1979) · 2022Review
- Pathogenesis of Primary Aldosteronism: Impact on Clinical Outcome.Frontiers in endocrinology · 2022Review
- Ion Channels in Cancer: Orchestrators of Electrical Signaling and Cellular Crosstalk.Reviews of physiology, biochemistry and pharmacology · 2022Review
- Progress on Genetic Basis of Primary Aldosteronism.Biomedicines · 2021Review
- Pathophysiological and Pharmacological Characteristics ofBiomedicines · 2021Article
- Molecular Mechanisms of Functional Adrenocortical Adenoma and Carcinoma: Genetic Characterization and Intracellular Signaling Pathway.Biomedicines · 2021Review
- GENETICS IN ENDOCRINOLOGY: Impact of race and sex on genetic causes of aldosterone-producing adenomas.European journal of endocrinology · 2021Review
- NP-59 Adrenal Scintigraphy as an Imaging Biomarker to PredictFrontiers in endocrinology · 2021Article
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 5 institutions in 2 countries.
Funding
Abstract
Aldosterone-producing adenomas (APAs) are benign tumors of the adrenal gland that constitutively produce the salt-retaining steroid hormone aldosterone and cause millions of cases of severe hypertension worldwide. Either of 2 somatic mutations in the potassium channel KCNJ5 (G151R and L168R, hereafter referred to as KCNJ5MUT) in adrenocortical cells account for half of APAs worldwide. These mutations alter channel selectivity to allow abnormal Na+ conductance, resulting in membrane depolarization, calcium influx, aldosterone production, and cell proliferation. Because APA diagnosis requires a difficult invasive procedure, patients often remain undiagnosed and inadequately treated. Inhibitors of KCNJ5MUT could allow noninvasive diagnosis and therapy of APAs carrying KCNJ5 mutations. Here, we developed a high-throughput screen for rescue of KCNJ5MUT-induced lethality and identified a series of macrolide antibiotics, including roxithromycin, that potently inhibit KCNJ5MUT, but not KCNJ5WT. Electrophysiology demonstrated direct KCNJ5MUT inhibition. In human aldosterone-producing adrenocortical cancer cell lines, roxithromycin inhibited KCNJ5MUT-induced induction of CYP11B2 (encoding aldosterone synthase) expression and aldosterone production. Further exploration of macrolides showed that KCNJ5MUT was similarly selectively inhibited by idremcinal, a macrolide motilin receptor agonist, and by synthesized macrolide derivatives lacking antibiotic or motilide activity. Macrolide-derived selective KCNJ5MUT inhibitors thus have the potential to advance the diagnosis and treatment of APAs harboring KCNJ5MUT.
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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.