ArticleNature communications2024
Structural basis of TRPV1 inhibition by SAF312 and cholesterol.
Article in Nature communications, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed.
- Cholesterol inhibits capsaicin activation of the TRPV1 channel.Channels (Austin, Tex.) · 2026Article
- Orally available Colivin traps TRPV3 in an inactive state and suppresses intestinal inflammation.The EMBO journal · 2026Article
- TRPV1‑mediated central sensitisation: Core mechanisms of migraine chronification and novel targeted therapeutic strategies (Review).International journal of molecular medicine · 2026Review
- Role of capsaicin, circadian clock genes, and TRPV1 in colorectal carcinogenesis: Lessons and future directions.Journal of advanced research · 2026Review
- TRPV1 antagonism occurs through diverse structural mechanisms.bioRxiv : the preprint server for biology · 2026Article
- Article
- Review
- Transient Receptor Potential (TRP) Channels as Fundamental Regulators of Fibrosis and Pruritus-A New Therapeutic Target for Pathological Scar Management.International journal of molecular sciences · 2026Review
- Perspectives on TRPV Channels in the Structural and Computational Revolution Era.Advances in experimental medicine and biology · 2026Review
- EGFR activation requires cholesterol interaction at the inner leaflet of the plasma membrane.Science advances · 2025Article
- Compound lidocaine cream with warm compress for pain relief in ultrasound-guided peripherally inserted central catheter placement for cancer patients.World journal of clinical oncology · 2025Article
- Structural basis of the inhibition of TRPV1 by analgesic sesquiterpenes.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Forty sites of TRP channel regulation.Current opinion in chemical biology · 2025Review
- Structure- and Ligand-Based Virtual Screening for Identification of Novel TRPV4 Antagonists.Molecules (Basel, Switzerland) · 2024Article
Corrections and comments
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Authors and funding
6 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Transient Receptor Potential Vanilloid 1 (TRPV1) plays a central role in pain sensation and is thus an attractive pharmacological drug target. SAF312 is a potent, selective, and non-competitive antagonist of TRPV1 and shows promising potential in treating ocular surface pain. However, the precise mechanism by which SAF312 inhibits TRPV1 remains poorly understood. Here, we present the cryo-EM structure of human TRPV1 in complex with SAF312, elucidating the structural foundation of its antagonistic effects on TRPV1. SAF312 binds to the vanilloid binding pocket, preventing conformational changes in S4 and S5 helices, which are essential for channel gating. Unexpectedly, a putative cholesterol was found to contribute to SAF312's inhibition. Complemented by mutagenesis experiments and molecular dynamics simulations, our research offers substantial mechanistic insights into the regulation of TRPV1 by SAF312, highlighting the interplay between the antagonist and cholesterol in modulating TRPV1 function. This work not only expands our understanding of TRPV1 inhibition by SAF312 but also lays the groundwork for further developments in the design and optimization of TRPV1-related therapies.
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Registered trials
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