ArticleBritish journal of pharmacology2015
Identification and optimization of 2-aminobenzimidazole derivatives as novel inhibitors of TRPC4 and TRPC5 channels.
Article in British journal of pharmacology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
What it found
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Who cites it
28 citing papers in PubMed, 47 citations in OpenAlex.
- NaThe Journal of membrane biology · 2026Article
- Metal Ion Signaling in Biomedicine.Chemical reviews · 2025Review
- TRPC4 deletion elicits behavioral defects in sociability by dysregulating expression of microRNA-138-2.iScience · 2024Article
- TRPC absence induces pro-inflammatory macrophage polarization to promote obesity and exacerbate colorectal cancer.Frontiers in pharmacology · 2024Article
- TRPV3: Structure, Diseases and Modulators.Molecules (Basel, Switzerland) · 2023Review
- TRPC channels as emerging targets for seizure disorders.Trends in pharmacological sciences · 2022Review
- Involvement of TRPC5 channels, inwardly rectifying KThe Journal of physiology · 2021Article
- Canonical transient receptor potential channels and their modulators: biology, pharmacology and therapeutic potentials.Archives of pharmacal research · 2021Review
- Article
- Blockade of TRPC Channels Limits Cholinergic-Driven Hyperexcitability and Seizure Susceptibility After Traumatic Brain Injury.Frontiers in neuroscience · 2021Article
- Review
- TRPC channels: Structure, function, regulation and recent advances in small molecular probes.Pharmacology & therapeutics · 2020Review
- Angiotensin-II-Evoked CaCells · 2020Article
- Contribution of TRPC Channels in Neuronal Excitotoxicity Associated With Neurodegenerative Disease and Ischemic Stroke.Frontiers in cell and developmental biology · 2020Article
- Treasure troves of pharmacological tools to study transient receptor potential canonical 1/4/5 channels.British journal of pharmacology · 2019Review
- Gq-Coupled Muscarinic Receptor Enhancement of KCNQ2/3 Channels and Activation of TRPC Channels in Multimodal Control of Excitability in Dentate Gyrus Granule Cells.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2019Article
- TRP Channels as Drug Targets to Relieve Itch.Pharmaceuticals (Basel, Switzerland) · 2018Review
- Pyrazolo[1,5-a]pyrimidine TRPC6 antagonists for the treatment of gastric cancer.Cancer letters · 2018Article
- Review
- Endothelial CaInternational journal of molecular sciences · 2018Review
Corrections and comments
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Authors and funding
15 authors at 6 institutions in 2 countries.
Funding
Abstract
background and purposeTransient receptor potential canonical (TRPC) channels play important roles in a broad array of physiological functions and are involved in various diseases. However, due to a lack of potent subtype-specific inhibitors the exact roles of TRPC channels in physiological and pathophysiological conditions have not been elucidated. EXPERIMENTAL APPROACH: Using fluorescence membrane potential and Ca(2+) assays and electrophysiological recordings, we characterized new 2-aminobenzimidazole-based small molecule inhibitors of TRPC4 and TRPC5 channels identified from cell-based fluorescence high-throughput screening. KEY
resultsThe original compound, M084, was a potent inhibitor of both TRPC4 and TRPC5, but was also a weak inhibitor of TRPC3. Structural modifications of the lead compound resulted in the identification of analogues with improved potency and selectivity for TRPC4 and TRPC5 channels. The aminobenzimidazole derivatives rapidly inhibited the TRPC4- and TRPC5-mediated currents when applied from the extracellular side and this inhibition was independent of the mode of activation of these channels. The compounds effectively blocked the plateau potential mediated by TRPC4-containing channels in mouse lateral septal neurons, but did not affect the activity of heterologously expressed TRPA1, TRPM8, TRPV1 or TRPV3 channels or that of the native voltage-gated Na(+) , K(+) and Ca(2) (+) channels in dissociated neurons. CONCLUSIONS AND IMPLICATIONS: The TRPC4/C5-selective inhibitors developed here represent novel and useful pharmaceutical tools for investigation of physiological and pathophysiological functions of TRPC4/C5 channels.
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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.