ArticleMolecular pharmacology2012
Structure-activity relationship of fenamates as Slo2.1 channel activators.
Article in Molecular pharmacology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 27 citations in OpenAlex.
- Slick K+ channels contribute to cardiac remodeling, fibrosis, and dysfunction in postinfarction hearts.JCI insight · 2026Article
- Nonsteroidal Anti-Inflammatory Drugs as Modulators of Cation Channels: Fenamates Repurposing in Channelopathies.ChemMedChem · 2025Review
- Inhibition of Fast Nerve Conduction Produced by Analgesics and Analgesic Adjuvants-Possible Involvement in Pain Alleviation.Pharmaceuticals (Basel, Switzerland) · 2020Review
- Mapping ligand binding pockets in chloride ClC-1 channels through an integrated in silico and experimental approach using anthracene-9-carboxylic acid and niflumic acid.British journal of pharmacology · 2018Article
- The Slo(w) path to identifying the mitochondrial channels responsible for ischemic protection.The Biochemical journal · 2017Review
- Molecular mechanisms of Slo2 KThe Journal of physiology · 2017Article
- International Union of Basic and Clinical Pharmacology. C. Nomenclature and Properties of Calcium-Activated and Sodium-Activated Potassium Channels.Pharmacological reviews · 2017Review
- Hydrophobic interactions between the S5 segment and the pore helix stabilizes the closed state of Slo2.1 potassium channels.Biochimica et biophysica acta · 2016Article
- Identification of the Intracellular Na+ Sensor in Slo2.1 Potassium Channels.The Journal of biological chemistry · 2015Article
- Administration of the nonsteroidal anti-inflammatory drug tolfenamic acid at embryo transfer improves maintenance of pregnancy and embryo survival in recipient mice.Journal of assisted reproduction and genetics · 2015Article
- Intracellular ATP does not inhibit Slo2.1 K+ channels.Physiological reports · 2014Article
- Niflumic acid affects store-operated Ca(2+)-permeable (SOC) and Ca (2+)-dependent K (+) and Cl (-) ion channels and induces apoptosis in K562 cells.The Journal of membrane biology · 2014Article
- Structural basis of ion permeation gating in Slo2.1 K+ channels.The Journal of general physiology · 2013Article
- Novel diuretic targets.American journal of physiology. Renal physiology · 2013Review
- Flufenamic acid as an ion channel modulator.Pharmacology & therapeutics · 2013Review
- Molecular basis of potassium channels in pancreatic duct epithelial cells.Channels (Austin, Tex.)Review
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Niflumic acid, 2-{[3-(trifluoromethyl)phenyl]amino}pyridine-3-carboxylic acid (NFA), a nonsteroidal anti-inflammatory drug that blocks cyclooxygenase (COX), was shown previously to activate [Na(+)](i)-regulated Slo2.1 channels. In this study, we report that other fenamates, including flufenamic acid, mefenamic acid, tolfenamic acid, meclofenamic acid, and a phenyl acetic acid derivative, diclofenac, also are low-potency (EC(50) = 80 μM to 2.1 mM), partial agonists of human Slo2.1 channels heterologously expressed in Xenopus oocytes. Substituent analysis determined that N-phenylanthranilic acid was the minimal pharmacophore for fenamate activation of Slo2.1 channels. The effects of fenamates were biphasic, with an initial rapid activation phase followed by a slow phase of current inhibition. Ibuprofen, a structurally dissimilar COX inhibitor, did not activate Slo2.1. Preincubation of oocytes with ibuprofen did not significantly alter the effects of NFA, suggesting that neither channel activation nor inhibition is associated with COX activity. A point mutation (A278R) in the pore-lining S6 segment of Slo2.1 increased the sensitivity to activation and reduced the inhibition induced by NFA. Together, our results suggest that fenamates bind to two sites on Slo2.1 channels: an extracellular accessible site to activate and a cytoplasmic accessible site in the pore to inhibit currents.
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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.