ArticleAdvanced science (Weinheim, Baden-Wurttemberg, Germany)2024
Structural Pharmacology of TRPV4 Antagonists.
Article in Advanced science (Weinheim, Baden-Wurttemberg, Germany), 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
What it found
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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
14 citing papers in PubMed, 16 citations in OpenAlex.
- Piezo-type mechanosensitive ion channel component 1: a mechano-bioenergetic transducer in the tumour microenvironment.Annals of medicine · 2026Review
- Phosgene inhalation injury in mice: Modeling human pathophysiology, biomarker discovery, and therapeutic target identification.Toxicology and applied pharmacology · 2026Article
- Danggui Sini Decoction Alleviates Sciatica by Reducing Peripheral Sensitization through Downregulation of Transient Receptor Potential Channels in Dorsal Root Ganglions.Chinese journal of integrative medicine · 2026Article
- TRPV4 drives macrophage pyroptosis via mitochondrial dysfunction and mtROS-dependent NLRP3 inflammasome activation in acute lung injury.Redox biology · 2026Article
- Symmetry-driven gating of TRPM8 by PIPNature communications · 2026Article
- TRPV4 inhibition as a pharmacotherapy for post-hemorrhagic hydrocephalus.Fluids and barriers of the CNS · 2026Article
- Role of transient receptor potential channels on pathogenesis and treatment of psoriasis.Inflammopharmacology · 2026Review
- Direct crosstalk between GPCRs and ion channels via G proteins.Experimental & molecular medicine · 2025Review
- Targeting TRPV4 to restore glymphatic system function and alleviate cerebral edema in ischemic stroke.Brain pathology (Zurich, Switzerland) · 2025Article
- TRPV4 Channel in Neurological Disease: from Molecular Mechanisms to Therapeutic Potential.Molecular neurobiology · 2025Review
- Forty sites of TRP channel regulation.Current opinion in chemical biology · 2025Review
- Structure- and Ligand-Based Virtual Screening for Identification of Novel TRPV4 Antagonists.Molecules (Basel, Switzerland) · 2024Article
- TRPV4-A Multifunctional Cellular Sensor Protein with Therapeutic Potential.Sensors (Basel, Switzerland) · 2024Review
- Structural Pharmacology of TRPV4 Antagonists.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 2 countries.
Funding
Abstract
The nonselective calcium-permeable Transient Receptor Potential Cation Channel Subfamily V Member4 (TRPV4) channel regulates various physiological activities. Dysfunction of TRPV4 is linked to many severe diseases, including edema, pain, gastrointestinal disorders, lung diseases, and inherited neurodegeneration. Emerging TRPV4 antagonists show potential clinical benefits. However, the molecular mechanisms of TRPV4 antagonism remain poorly understood. Here, cryo-electron microscopy (cryo-EM) structures of human TRPV4 are presented in-complex with two potent antagonists, revealing the detailed binding pockets and regulatory mechanisms of TRPV4 gating. Both antagonists bind to the voltage-sensing-like domain (VSLD) and stabilize the channel in closed states. These two antagonists induce TRPV4 to undergo an apparent fourfold to twofold symmetry transition. Moreover, it is demonstrated that one of the antagonists binds to the VSLD extended pocket, which differs from the canonical VSLD pocket. Complemented with functional and molecular dynamics simulation results, this study provides crucial mechanistic insights into TRPV4 regulation by small-molecule antagonists, which may facilitate future drug discovery targeting TRPV4.
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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.