ArticleEuropean journal of pharmacology2014
Identification of novel small molecule modulators of K2P18.1 two-pore potassium channel.
Article in European journal of pharmacology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
What it found
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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
18 citing papers in PubMed, 36 citations in OpenAlex.
- The research progress into cellular mechanosensitive ion channels mediating cancer pain.Channels (Austin, Tex.) · 2025Review
- Development of Non-opioid Analgesics Targeting Two-pore Domain Potassium Channels.Current neuropharmacology · 2022Review
- Two-Pore-Domain Potassium (KCells · 2021Review
- Structural Insights into the Mechanisms and Pharmacology of KJournal of molecular biology · 2021Review
- Block of TREK and TRESK K2P channels by lamotrigine and two derivatives sipatrigine and CEN-092.Biochemistry and biophysics reports · 2021Article
- 5-(Indol-2-yl)pyrazolo[3,4-Molecules (Basel, Switzerland) · 2021Article
- A causal role for TRESK loss of function in migraine mechanisms.Brain : a journal of neurology · 2019Article
- Pharmacologically reversible, loss of function mutations in the TM2 and TM4 inner pore helices of TREK-1 K2P channels.Scientific reports · 2019Article
- Discovery of Novel TASK-3 Channel Blockers Using a Pharmacophore-Based Virtual Screening.International journal of molecular sciences · 2019Article
- The Role of TRESK in Discrete Sensory Neuron Populations and Somatosensory Processing.Frontiers in molecular neuroscience · 2019Article
- Verapamil Inhibits TRESK (KInternational journal of molecular sciences · 2018Article
- Selective and state-dependent activation of TRESK (KBritish journal of pharmacology · 2017Article
- Aristolochic acid, a plant extract used in the treatment of pain and linked to Balkan endemic nephropathy, is a regulator of K2P channels.British journal of pharmacology · 2016Article
- High throughput screening technologies for ion channels.Acta pharmacologica Sinica · 2016Review
- Activation of TRESK channels by the inflammatory mediator lysophosphatidic acid balances nociceptive signalling.Scientific reports · 2015Article
- Two-pore domain potassium channels: potential therapeutic targets for the treatment of pain.Pflugers Archiv : European journal of physiology · 2015Review
- Properties, regulation, pharmacology, and functions of the K₂p channel, TRESK.Pflugers Archiv : European journal of physiology · 2015Review
- Placing ion channels into a signaling network of T cells: from maturing thymocytes to healthy T lymphocytes or leukemic T lymphoblasts.BioMed research international · 2015Review
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Two-pore domain potassium (K2P) channels are responsible for background potassium (K+) current, which is crucial for the maintenance of resting membrane potential. K2P18.1, also called TWIK-related spinal cord K+ channel (TRESK) or KCNK18, is thought to be a major contributor to background K+ currents, particularly in sensory neurons where it is abundantly expressed. Despite its critical role and potential therapeutic implication, pharmacological tools for probing K2P18.1 activity remain unavailable. Here, we report a high-throughput screen against a collection of bioactive compounds that yielded 26 inhibitors and 8 activators of K2P18.1 channel activity with more than 10-fold selectivity over the homologous channel K2P9.1. Among these modulators, the antihistamine loratadine inhibited K2P18.1 activity with IC50 of 0.49±0.23 µM and is considerably more potent than existing K2P18.1 inhibitors. Importantly, the inhibition by loratadine remains equally efficacious upon potentiation of K2P18.1 by calcium signaling. Furthermore, the loratadine effect is dependent on transmembrane residues F145 and F352, providing orthogonal evidence that the inhibition is caused by a direct compound-channel interaction. This study reveals new pharmacological modulators of K2P18.1 activity useful in dissecting native K2P18.1 function.
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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.