ArticleNature chemical biology2025
Mechanism of capsaicin entry into buried vanilloid sites in TRPV1.
Article in Nature chemical biology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 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
9 citing papers in PubMed.
- Substrate recognition and allosteric inhibition of human betaine/GABA transporter 1.Nature communications · 2026Article
- Calpain cleaves the distal carboxyl terminus of TRPV1 and modulates its tachyphylaxis.Cell & bioscience · 2026Article
- Arvanil reverses cisplatin resistance in ovarian cancer by activating HMOX1-driven ferroptosis.Scientific reports · 2026Article
- TRPV1 antagonism occurs through diverse structural mechanisms.bioRxiv : the preprint server for biology · 2026Article
- 5'untranslated regions provide a versatile toolkit for tunable exogenous protein expression.Molecular biology of the cell · 2026Article
- Structure of the human P2X3 receptor reveals the basis for subtype-selective inhibition by sivopixant.PLoS biology · 2026Article
- NIR-activated adipose-targeted nanocarrier drives local browning and metabolic restoration.Regenerative biomaterials · 2026Article
- Receptors from an ADAR trick.Nature chemical biology · 2025Article
- RAS signaling gets granular.Nature chemical biology · 2025Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
19 authors.
Funding
Abstract
The transient receptor potential vanilloid 1 (TRPV1) receptor is a promising target for nonopioid analgesics, yet hyperthermic side effects have hindered drug development. The prevailing perspective maintains that extracellular hydrophobic vanilloid ligands, such as capsaicin, traverse the cell membrane to reach the buried vanilloid site during TRPV1 activation. Here, we present an alternative mechanism based on computational and experimental approaches, which suggests a distinct hydrophobic pathway at the TRPV1-cell membrane interface as the principal route for ligand entry to the vanilloid site, rather than direct membrane penetration. Modifications to residues within this pathway greatly delayed capsaicin entry without directly modulating TRPV1 channel gating. A compound designed to occupy this pathway's entrance exhibited analgesic effects without inducing hyperthermia. Cryo-electron microscopy confirmed binding to TRPV1 and its role in perturbing capsaicin entry. Thus, our findings unveil a unique and targetable route for capsaicin access to the TRPV1 vanilloid site.
Indexed as
Identifiers
40702302What 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.