ArticleeLife2020
Structural basis for pharmacological modulation of the TRPC6 channel.
Article in eLife, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 61 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.
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Who cites it
61 citing papers in PubMed, 115 citations in OpenAlex.
- Functional evaluation of TRPC6 missense variants in cancer patients via molecular docking analysis compared with patch Clamp electrophysiology.The Journal of biological chemistry · 2026Article
- Gain-of-Function VariantCirculation. Genomic and precision medicine · 2026Article
- Review
- Functional Evaluation ofbioRxiv : the preprint server for biology · 2026Article
- Molecular architecture of the human TRPC1/C5 heteromeric channel.Nature communications · 2025Article
- Physiological functions and pharmacological targeting of transient receptor potential channels.Pharmacological reviews · 2025Review
- Structural mechanism of the agonist binding on human TRPC3 channel.Nature communications · 2025Article
- Structure-Guided Discovery of Benzoic-Acid-Based TRPC6 Ligands: An Integrated Docking, MD, and MM-GBSA SAR Study: Potential Therapeutic Molecules for Autism Spectrum Disorder.Pharmaceuticals (Basel, Switzerland) · 2025Article
- Structural and accessibility studies highlight the differential binding of clemizole to TRPC5 and TRPC6.Journal of biomolecular structure & dynamics · 2025Article
- Natural History and Clinicopathological Associations of TRPC6-Associated Podocytopathy.Journal of the American Society of Nephrology : JASN · 2025Article
- Forty sites of TRP channel regulation.Current opinion in chemical biology · 2025Review
- Notoginsenoside R1 Improved Hypoxic Pulmonary Hypertension by Inhibiting Glycolysis-Mediated Pulmonary Arterial Vascular Remodeling.Canadian respiratory journal · 2025Article
- Anesthetic- and Analgesic-Related Drugs Modulating Both Voltage-Gated NaBiomolecules · 2024Review
- Article
- Functional determinants of lysophospholipid- and voltage-dependent regulation of TRPC5 channel.Cellular and molecular life sciences : CMLS · 2024Article
- Conservation of the cooling agent binding pocket within the TRPM subfamily.bioRxiv : the preprint server for biology · 2024Article
- Calcium signalling and transport in the kidney.Nature reviews. Nephrology · 2024Review
- PCC0208057 as a small molecule inhibitor of TRPC6 in the treatment of prostate cancer.Frontiers in pharmacology · 2024Article
- Review
- Pathophysiology and pathogenic mechanisms of pulmonary hypertension: role of membrane receptors, ion channels, and CaPhysiological reviews · 2023Review
1 more citing papers are in PubMed but not listed here.
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 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Transient receptor potential canonical (TRPC) proteins form nonselective cation channels that play physiological roles in a wide variety of cells. Despite growing evidence supporting the therapeutic potential of TRPC6 inhibition in treating pathological cardiac and renal conditions, mechanistic understanding of TRPC6 function and modulation remains obscure. Here we report cryo-EM structures of TRPC6 in both antagonist-bound and agonist-bound states. The structures reveal two novel recognition sites for the small-molecule modulators corroborated by mutagenesis data. The antagonist binds to a cytoplasm-facing pocket formed by S1-S4 and the TRP helix, whereas the agonist wedges at the subunit interface between S6 and the pore helix. Conformational changes upon ligand binding illuminate a mechanistic rationale for understanding TRPC6 modulation. Furthermore, structural and mutagenesis analyses suggest several disease-related mutations enhance channel activity by disrupting interfacial interactions. Our results provide principles of drug action that may facilitate future design of small molecules to ameliorate TRPC6-mediated diseases.
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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.