ArticleProceedings of the National Academy of Sciences of the United States of America2009
Selective and direct inhibition of TRPC3 channels underlies biological activities of a pyrazole compound.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 186 papers.
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186 citing papers in PubMed, 383 citations in OpenAlex.
- Pyrazole-derived TRPC3 antagonist ameliorates synaptic dysfunctions and memory deficits in Alzheimer's disease models.Molecular psychiatry · 2026Article
- IPbioRxiv : the preprint server for biology · 2026Article
- Increased Arrhythmic Risk in Obesity Is Transduced by Adipose Tissue-Derived Extracellular Vesicles.JACC. Basic to translational science · 2026Article
- Selective TRPV2 Antagonists Derived from the Natural Product Piperlongumine Inhibit Cancer Cell Migration and Metastasis.ACS chemical biology · 2026Article
- Functional and structural basis of a hypermorphic TRPC3 variant.Science advances · 2026Article
- Review
- Inhibition of TRPC3-Nox2 Complex Formation Ameliorates Skeletal Muscle Atrophy.Antioxidants (Basel, Switzerland) · 2025Article
- Physiological functions and pharmacological targeting of transient receptor potential channels.Pharmacological reviews · 2025Review
- Flufenamic acid reduces alveolar bone loss and pyrazole 3 enhances alveolar bone recovery in periodontitis mice.Journal of veterinary science · 2025Article
- Targeting TRPC-5 Channel Inhibition to Improve Penile Vascular Function in Erectile Dysfunction.International journal of molecular sciences · 2025Article
- TRPC3 inhibition induces myofibroblast differentiation in diabetic dermal fibroblasts.Frontiers in physiology · 2025Article
- Discovery of a potent and selective TRPC3 antagonist with neuroprotective effects.Bioorganic & medicinal chemistry · 2025Article
- TRP channels in epileptogenesis: calcium dysregulation mechanisms and pharmacological targeting strategies.Frontiers in molecular neuroscience · 2025Review
- Pathophysiological significance and modulation of the transient receptor potential canonical 3 ion channel.Medicinal research reviews · 2024Review
- Weighted single step GWAS reveals genomic regions associated with economic traits in Murrah buffaloes.Animal biotechnology · 2024Article
- CaBiomolecules · 2024Review
- Generation and Characterization of Three Novel Mouse Mutant Strains Susceptible to Audiogenic Seizures.Cells · 2024Article
- Neuronal Nitric Oxide Synthase Regulates Cerebellar Parallel Fiber Slow EPSC in Purkinje Neurons by Modulating STIM1-Gated TRPC3-Containing Channels.Cerebellum (London, England) · 2024Article
- TRPC3 signalling contributes to the biogenesis of extracellular vesicles.Journal of extracellular biology · 2024Article
- A role for TRPC3 in mammalian testis development.Frontiers in cell and developmental biology · 2024Article
126 more citing papers are in PubMed but not listed here.
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Authors and funding
22 authors at 7 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Canonical transient receptor potential (TRPC) channels control influxes of Ca(2+) and other cations that induce diverse cellular processes upon stimulation of plasma membrane receptors coupled to phospholipase C (PLC). Invention of subtype-specific inhibitors for TRPCs is crucial for distinction of respective TRPC channels that play particular physiological roles in native systems. Here, we identify a pyrazole compound (Pyr3), which selectively inhibits TRPC3 channels. Structure-function relationship studies of pyrazole compounds showed that the trichloroacrylic amide group is important for the TRPC3 selectivity of Pyr3. Electrophysiological and photoaffinity labeling experiments reveal a direct action of Pyr3 on the TRPC3 protein. In DT40 B lymphocytes, Pyr3 potently eliminated the Ca(2+) influx-dependent PLC translocation to the plasma membrane and late oscillatory phase of B cell receptor-induced Ca(2+) response. Moreover, Pyr3 attenuated activation of nuclear factor of activated T cells, a Ca(2+)-dependent transcription factor, and hypertrophic growth in rat neonatal cardiomyocytes, and in vivo pressure overload-induced cardiac hypertrophy in mice. These findings on important roles of native TRPC3 channels are strikingly consistent with previous genetic studies. Thus, the TRPC3-selective inhibitor Pyr3 is a powerful tool to study in vivo function of TRPC3, suggesting a pharmaceutical potential of Pyr3 in treatments of TRPC3-related diseases such as cardiac hypertrophy.
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