ArticleScientific reports2016
Small molecule dual-inhibitors of TRPV4 and TRPA1 for attenuation of inflammation and pain.
Article in Scientific reports, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.
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Who cites it
45 citing papers in PubMed, 79 citations in OpenAlex.
- Rewiring Atopic Dermatitis: Alarmin Cytokines at the Core of Barrier-Immune-Neuro-Microbiome Networks.Clinical reviews in allergy & immunology · 2026Review
- 25+ Years of TRPV4: From Discovery to Translational Horizons.Research square · 2026Article
- Identification of Phialomustin‑B (PHL-B) as a Novel Natural TRPA1 Channel Inhibitor.ACS omega · 2025Article
- Crosstalk between calcium and reactive oxygen species signaling in cancer revisited.Cell calcium · 2025Review
- Skeletal dysplasia-causing mutations in TRPV4 alter the chondrocyte transcriptomic response to mechanical loading.American journal of physiology. Cell physiology · 2025Article
- Ion Currents Mediated by TRPA1 Channels in Freshly Dissociated Rat Articular Chondrocytes: Biophysical Properties and Regulation by Inflammatory Processes.Pharmaceuticals (Basel, Switzerland) · 2025Article
- Identification of Novel Selective Transient Receptor Potential Vanilloid 4 (TRPV4) Agonists.Current pharmaceutical design · 2025Article
- Structure- and Ligand-Based Virtual Screening for Identification of Novel TRPV4 Antagonists.Molecules (Basel, Switzerland) · 2024Article
- Targeting TRPV4 Channels for Cancer Pain Relief.Cancers · 2024Review
- The Role of the TRPV4 Channel in Intestinal Physiology and Pathology.Journal of inflammation research · 2024Review
- Unconventional interactions of the TRPV4 ion channel with beta-adrenergic receptor ligands.Life science alliance · 2023Article
- Article
- Modulation of TRPV4 protects against degeneration induced by sustained loading and promotes matrix synthesis in the intervertebral disc.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2023Article
- Molecular mechanisms of pain in acute pancreatitis: recent basic research advances and therapeutic implications.Frontiers in molecular neuroscience · 2023Review
- Building a Co-ordinated Musculoskeletal System: The Plasticity of the Developing Skeleton in Response to Muscle Contractions.Advances in anatomy, embryology, and cell biology · 2023Article
- Piezo1-mediated stellate cell activation causes pressure-induced pancreatic fibrosis in mice.JCI insight · 2022Article
- Advances in TRP channel drug discovery: from target validation to clinical studies.Nature reviews. Drug discovery · 2022Review
- Spinal cord dorsal horn sensory gate in preclinical models of chemotherapy-induced painful neuropathy and contact dermatitis chronic itch becomes less leaky withFrontiers in molecular neuroscience · 2022Article
- Regulation of chondrocyte biosynthetic activity by dynamic hydrostatic pressure: the role of TRP channels.Connective tissue research · 2022Article
- Transient receptor potential vanilloid 4 as a regulator of induced pluripotent stem cell chondrogenesis.Stem cells (Dayton, Ohio) · 2021Article
Corrections and comments
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Authors and funding
15 authors at 2 institutions in 1 country.
Funding
Abstract
TRPV4 ion channels represent osmo-mechano-TRP channels with pleiotropic function and wide-spread expression. One of the critical functions of TRPV4 in this spectrum is its involvement in pain and inflammation. However, few small-molecule inhibitors of TRPV4 are available. Here we developed TRPV4-inhibitory molecules based on modifications of a known TRPV4-selective tool-compound, GSK205. We not only increased TRPV4-inhibitory potency, but surprisingly also generated two compounds that potently co-inhibit TRPA1, known to function as chemical sensor of noxious and irritant signaling. We demonstrate TRPV4 inhibition by these compounds in primary cells with known TRPV4 expression - articular chondrocytes and astrocytes. Importantly, our novel compounds attenuate pain behavior in a trigeminal irritant pain model that is known to rely on TRPV4 and TRPA1. Furthermore, our novel dual-channel blocker inhibited inflammation and pain-associated behavior in a model of acute pancreatitis - known to also rely on TRPV4 and TRPA1. Our results illustrate proof of a novel concept inherent in our prototype compounds of a drug that targets two functionally-related TRP channels, and thus can be used to combat isoforms of pain and inflammation in-vivo that involve more than one TRP channel. This approach could provide a novel paradigm for treating other relevant health conditions.
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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.