ArticleScience advances2020
Inactivation-mimicking block of the epithelial calcium channel TRPV6.
Article in Science advances, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 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
26 citing papers in PubMed, 42 citations in OpenAlex.
- Open-channel block of human TRPV6 by polyamine spermine.Nature communications · 2026Article
- TRPV6-Mediated CaCancers · 2026Review
- Molecular mechanism of menthol-induced TRPV5 channel inhibition.Nature communications · 2026Article
- Discovery of the small molecular inhibitors against TRPV6 as potential anti-cancer agents by structural based virtual screening.Frontiers in chemistry · 2026Article
- The locking mechanism of human TRPV6 inhibition by intracellular magnesium.Nature communications · 2025Article
- Physiological functions and pharmacological targeting of transient receptor potential channels.Pharmacological reviews · 2025Review
- TRPV6 channel function is involved in endometrial epithelial cell CaCellular and molecular life sciences : CMLS · 2025Article
- Molecular basis of TRPV3 channel blockade by intracellular polyamines.Communications biology · 2025Article
- Calcium channels as pharmacological targets for cancer therapy.Clinical and experimental medicine · 2025Review
- The Molecular Biology of Placental Transport of Calcium to the Human Foetus.International journal of molecular sciences · 2025Review
- Structure-function analyses of human TRPV6 ancestral and derived haplotypes.Structure (London, England : 1993) · 2025Article
- Inhibition of NMDA receptors and other ion channel types by membrane-associated drugs.Frontiers in pharmacology · 2025Review
- The endocannabinoid system in bovine tissues: characterization of transcript abundance in the growing Holstein steer.BMC veterinary research · 2024Article
- Dynamic molecular portraits of ion-conducting pores characterize functional states of TRPV channels.Communications chemistry · 2024Article
- Bidirectional Allosteric Coupling between PIPInternational journal of molecular sciences · 2024Article
- Calcium binding and permeation in TRPV channels: Insights from molecular dynamics simulations.The Journal of general physiology · 2023Article
- Molecular pharmacology of the onco-TRP channel TRPV6.Channels (Austin, Tex.) · 2023Review
- Molecular pathway and structural mechanism of human oncochannel TRPV6 inhibition by the phytocannabinoid tetrahydrocannabivarin.Nature communications · 2023Article
- Structure of human TRPV4 in complex with GTPase RhoA.Nature communications · 2023Article
- Structural mechanism of human oncochannel TRPV6 inhibition by the natural phytoestrogen genistein.Nature communications · 2023Article
Corrections and comments
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Authors and funding
12 authors at 4 institutions in 4 countries.
Funding
Abstract
Epithelial calcium channel TRPV6 plays vital roles in calcium homeostasis, and its dysregulation is implicated in multifactorial diseases, including cancers. Here, we study the molecular mechanism of selective nanomolar-affinity TRPV6 inhibition by (4-phenylcyclohexyl)piperazine derivatives (PCHPDs). We use x-ray crystallography and cryo-electron microscopy to solve the inhibitor-bound structures of TRPV6 and identify two types of inhibitor binding sites in the transmembrane region: (i) modulatory sites between the S1-S4 and pore domains normally occupied by lipids and (ii) the main site in the ion channel pore. Our structural data combined with mutagenesis, functional and computational approaches suggest that PCHPDs plug the open pore of TRPV6 and convert the channel into a nonconducting state, mimicking the action of calmodulin, which causes inactivation of TRPV6 channels under physiological conditions. This mechanism of inhibition explains the high selectivity and potency of PCHPDs and opens up unexplored avenues for the design of future-generation biomimetic drugs.
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What OpenQuestion holds
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.