ArticleNature communications2022
Inhibition mechanism of the chloride channel TMEM16A by the pore blocker 1PBC.
Article in Nature communications, 2022. 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
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
18 citing papers in PubMed, 27 citations in OpenAlex.
- Conformational changes upon pore blocker removal reveal conductive states of TMEM16A.bioRxiv : the preprint server for biology · 2026Article
- Exploring the selective inhibitory effects of Flavoxate and its analogues on two chloride channels and neuronal action potentials.The Korean journal of physiology & pharmacology : official journal of the Korean Physiological Society and the Korean Society of Pharmacology · 2026Article
- Article
- Simulation-based survey of TMEM16 family reveals that robust lipid scrambling requires an open groove.eLife · 2025Article
- Groove architecture controls lipid scrambling in simulations of protein and model systems.bioRxiv : the preprint server for biology · 2025Article
- Calcium-activated chloride channel TMEM16A opens via pi-helical transition in transmembrane segment 4.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Identification of novel TMEM16A blockers through integrated virtual screening, molecular dynamics, and experimental studies.Scientific reports · 2025Article
- Simulation-based survey of TMEM16 family reveals that robust lipid scrambling requires an open groove.bioRxiv : the preprint server for biology · 2025Article
- DTIAM: a unified framework for predicting drug-target interactions, binding affinities and drug mechanisms.Nature communications · 2025Article
- Wide-ranging cellular functions of ion channels and lipid scramblases in the structurally related TMC, TMEM16 and TMEM63 families.Nature structural & molecular biology · 2025Review
- TMEM16F regulates pathologic α-synuclein secretion and spread in cellular and mouse models of Parkinson's disease.Aging cell · 2025Article
- Tamsulosin ameliorates bone loss by inhibiting the release of ClProceedings of the National Academy of Sciences of the United States of America · 2025Article
- Vitexicarpin suppresses colorectal and non-small cell lung cancer via selective inhibition of Anoctamin 1.Frontiers in pharmacology · 2025Article
- Distinct modulation of calcium-activated chloride channel TMEM16A by drug-binding sites.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- TMEM16 proteins: CaInternational journal of molecular medicine · 2024Review
- Mechanistic basis of ligand efficacy in the calcium-activated chloride channel TMEM16A.The EMBO journal · 2023Article
- Identification of a drug binding pocket in TMEM16F calcium-activated ion channel and lipid scramblase.Nature communications · 2023Article
- Structural basis for the activation of the lipid scramblase TMEM16F.Nature communications · 2022Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
TMEM16A, a calcium-activated chloride channel involved in multiple cellular processes, is a proposed target for diseases such as hypertension, asthma, and cystic fibrosis. Despite these therapeutic promises, its pharmacology remains poorly understood. Here, we present a cryo-EM structure of TMEM16A in complex with the channel blocker 1PBC and a detailed functional analysis of its inhibition mechanism. A pocket located external to the neck region of the hourglass-shaped pore is responsible for open-channel block by 1PBC and presumably also by its structural analogs. The binding of the blocker stabilizes an open-like conformation of the channel that involves a rearrangement of several pore helices. The expansion of the outer pore enhances blocker sensitivity and enables 1PBC to bind at a site within the transmembrane electric field. Our results define the mechanism of inhibition and gating and will facilitate the design of new, potent TMEM16A modulators.
Indexed as
Identifiers
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.