ArticleScientific reports2017
Novel selective, potent naphthyl TRPM8 antagonists identified through a combined ligand- and structure-based virtual screening approach.
Article in Scientific reports, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 43 citations in OpenAlex.
- Direct modulation of TRPM8 ion channels by rapamycin and analog macrolide immunosuppressants.eLife · 2025Article
- An adamantane-based ligand as a novel chemical tool for thermosensory TRPM8 channel therapeutic modulation.The FEBS journal · 2025Article
- Article
- Conservation of the cooling agent binding pocket within the TRPM subfamily.bioRxiv : the preprint server for biology · 2024Article
- Ensemble of structure and ligand-based classification models for hERG liability profiling.Frontiers in pharmacology · 2023Article
- Molecular determinants of TRPM8 function: key clues for a cool modulation.Frontiers in pharmacology · 2023Review
- Mutations of TRPM8 channels: Unraveling the molecular basis of activation by cold and ligands.Medicinal research reviews · 2022Review
- Benzalkonium chloride, a common ophthalmic preservative, compromises rat corneal cold sensitive nerve activity.The ocular surface · 2022Article
- Extensive Sampling of Molecular Dynamics Simulations to Identify Reliable Protein Structures for Optimized Virtual Screening Studies: The Case of the hTRPM8 Channel.International journal of molecular sciences · 2022Article
- In Vitro and In Vivo Pharmacological Characterization of a Novel TRPM8 Inhibitor Chemotype Identified by Small-Scale Preclinical Screening.International journal of molecular sciences · 2022Article
- MetaClass, a Comprehensive Classification System for Predicting the Occurrence of Metabolic Reactions Based on the MetaQSAR Database.Molecules (Basel, Switzerland) · 2021Article
- TRPM8 Channels: Advances in Structural Studies and Pharmacological Modulation.International journal of molecular sciences · 2021Review
- Involvement of Opioid System and TRPM8/TRPA1 Channels in the Antinociceptive Effect ofBiomolecules · 2021Article
- Phenylalanine-Derived β-Lactam TRPM8 Modulators. Configuration Effect on the Antagonist Activity.International journal of molecular sciences · 2021Article
- Highly functionalized β-lactams and 2-ketopiperazines as TRPM8 antagonists with antiallodynic activity.Scientific reports · 2020Article
- Repositioning Dequalinium as Potent Muscarinic Allosteric Ligand by Combining Virtual Screening Campaigns and Experimental Binding Assays.International journal of molecular sciences · 2020Article
- Combining Molecular Dynamics and Docking Simulations to Develop Targeted Protocols for Performing Optimized Virtual Screening Campaigns on The hTRPM8 Channel.International journal of molecular sciences · 2020Article
- Characterization of New TRPM8 Modulators in Pain Perception.International journal of molecular sciences · 2019Article
- Recent Progress in TRPM8 Modulation: An Update.International journal of molecular sciences · 2019Review
- TRP Channels as Lower Urinary Tract Sensory Targets.Medical sciences (Basel, Switzerland) · 2019Review
Corrections and comments
- Erratum issued
Authors and funding
15 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Transient receptor potential melastatin 8 (TRPM8), a nonselective cation channel, is the predominant mammalian cold temperature thermosensor and it is activated by cold temperatures and cooling compounds, such as menthol and icilin. Because of its role in cold allodynia, cold hyperalgesia and painful syndromes TRPM8 antagonists are currently being pursued as potential therapeutic agents for the treatment of pain hypersensitivity. Recently TRPM8 has been found in subsets of bladder sensory nerve fibres, providing an opportunity to understand and treat chronic hypersensitivity. However, most of the known TRPM8 inhibitors lack selectivity, and only three selective compounds have reached clinical trials to date. Here, we applied two virtual screening strategies to find new, clinics suitable, TRPM8 inhibitors. This strategy enabled us to identify naphthyl derivatives as a novel class of potent and selective TRPM8 inhibitors. Further characterization of the pharmacologic properties of the most potent compound identified, compound 1, confirmed that it is a selective, competitive antagonist inhibitor of TRPM8. Compound 1 also proved itself active in a overreactive bladder model in vivo. Thus, the novel naphthyl derivative compound identified here could be optimized for clinical treatment of pain hypersensitivity in bladder disorders but also in different other pathologies.
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