ArticleBritish journal of pharmacology2013
NS6180, a new K(Ca) 3.1 channel inhibitor prevents T-cell activation and inflammation in a rat model of inflammatory bowel disease.
Article in British journal of pharmacology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 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
39 citing papers in PubMed, 66 citations in OpenAlex.
- Gut sensory neurons as regulators of neuro-immune-microbial interactions: from molecular mechanisms to precision therapy for IBD/IBS.Journal of neuroinflammation · 2025Review
- Design and structural basis of selective 1,4-dihydropyridine inhibitors of the calcium-activated potassium channel KProceedings of the National Academy of Sciences of the United States of America · 2025Article
- Article
- Challenges in the Therapeutic Targeting of KCa Channels: From Basic Physiology to Clinical Applications.International journal of molecular sciences · 2024Review
- Reduction of CaCells · 2023Article
- Ion channel regulation of gut immunity.The Journal of general physiology · 2023Article
- Pose Classification Using Three-Dimensional Atomic Structure-Based Neural Networks Applied to Ion Channel-Ligand Docking.Journal of chemical information and modeling · 2022Review
- The contribution of ion channels to shaping macrophage behaviour.Frontiers in pharmacology · 2022Review
- The Molecular Basis for the Calcium-Dependent Slow Afterhyperpolarization in CA1 Hippocampal Pyramidal Neurons.Frontiers in physiology · 2021Review
- Pharmacology of Small- and Intermediate-Conductance Calcium-Activated Potassium Channels.Annual review of pharmacology and toxicology · 2020Review
- Critical regulation of atherosclerosis by the KCa3.1 channel and the retargeting of this therapeutic target in in-stent neoatherosclerosis.Journal of molecular medicine (Berlin, Germany) · 2019Review
- Modulation of Cardiovascular Function in Primary Hypertension in Rat by SKA-31, an Activator ofInternational journal of molecular sciences · 2019Article
- Identification of Clotrimazole Derivatives as Specific Inhibitors of Arenavirus Fusion.Journal of virology · 2019Article
- KCa3.1 Transgene Induction in Murine Intestinal Epithelium Causes Duodenal Chyme Accumulation and Impairs Duodenal Contractility.International journal of molecular sciences · 2019Article
- Histone Deacetylases Enhance CaInternational journal of molecular sciences · 2018Article
- Activation mechanism of a human SK-calmodulin channel complex elucidated by cryo-EM structures.Science (New York, N.Y.) · 2018Article
- KCa3.1 Channel Modulators as Potential Therapeutic Compounds for Glioblastoma.Current neuropharmacology · 2018Article
- The Somatostatin Receptor-4 Agonist J-2156 Alleviates Mechanical Hypersensitivity in a Rat Model of Breast Cancer Induced Bone Pain.Frontiers in pharmacology · 2018Article
- Differences in ion channel phenotype and function between humans and animal models.Frontiers in bioscience (Landmark edition) · 2018Review
- Structural Determinants for the Selectivity of the Positive KCa3.1 Gating Modulator 5-Methylnaphtho[2,1-Molecular pharmacology · 2017Article
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 2 institutions in 2 countries.
Funding
Abstract
background and purposeThe K(Ca) 3.1 channel is a potential target for therapy of immune disease. We identified a compound from a new chemical class of K(Ca) 3.1 inhibitors and assessed in vitro and in vivo inhibition of immune responses. EXPERIMENTAL APPROACH: We characterized the benzothiazinone NS6180 (4-[[3-(trifluoromethyl)phenyl]methyl]-2H-1,4-benzothiazin-3(4H)-one) with respect to potency and molecular site of action on K(Ca) 3.1 channels, selectivity towards other targets, effects on T-cell activation as well as pharmacokinetics and inflammation control in colitis induced by 2,4-dinitrobenzene sulfonic acid, a rat model of inflammatory bowel disease (IBD). KEY
resultsNS6180 inhibited cloned human K(Ca) 3.1 channels (IC(50) = 9 nM) via T250 and V275, the same amino acid residues conferring sensitivity to triarylmethanes such as like TRAM-34. NS6180 inhibited endogenously expressed K(Ca) 3.1 channels in human, mouse and rat erythrocytes, with similar potencies (15-20 nM). NS6180 suppressed rat and mouse splenocyte proliferation at submicrolar concentrations and potently inhibited IL-2 and IFN-γ production, while exerting smaller effects on IL-4 and TNF-α and no effect on IL-17 production. Antibody staining showed K(Ca) 3.1 channels in healthy colon and strong up-regulation in association with infiltrating immune cells after induction of colitis. Despite poor plasma exposure, NS6180 (3 and 10 mg·kg(-1) b.i.d.) dampened colon inflammation and improved body weight gain as effectively as the standard IBD drug sulfasalazine (300 mg·kg(-1) q.d.). CONCLUSIONS AND IMPLICATIONS: NS6180 represents a novel class of K(Ca) 3.1 channel inhibitors which inhibited experimental colitis, suggesting K(Ca) 3.1 channels as targets for pharmacological control of intestinal inflammation.
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.