Inhibition of TRPV1 by an antagonist in clinical trials is dependent on cholesterol binding

IF 4.3 2区 生物学 Q2 CELL BIOLOGY Cell calcium Pub Date : 2024-09-25 DOI:10.1016/j.ceca.2024.102957
Tal Brandwine-Shemmer , Baruch Minke , Irena Levitan
{"title":"Inhibition of TRPV1 by an antagonist in clinical trials is dependent on cholesterol binding","authors":"Tal Brandwine-Shemmer ,&nbsp;Baruch Minke ,&nbsp;Irena Levitan","doi":"10.1016/j.ceca.2024.102957","DOIUrl":null,"url":null,"abstract":"<div><div>TRP Vanilloid 1 (TRPV1) channel, one of the major members of the TRP family was discovered to play a critical role in pain sensation, particularly inflammatory pain, and is associated with hyperalgesia, an enhanced sensitivity to pain. A new study by <em><u>Fan</u></em> <u>et al.</u> <em><u>“</u><u>Structural basis of TRPV1 inhibition by SAF312 and cholesterol</u></em>” sheds new light on the mechanistic structural basis of TRPV1 inhibition by SAF312 (Libvatrep), a TRPV1 antagonist, currently in phase II clinical trials. They discover that the binding site of SAF312 in TRPV1 is in close vicinity and partially overlaps with the binding site of cholesterol and that removal of cholesterol interferes with the ability of SAF312 to suppress TRPV1 current.</div></div>","PeriodicalId":9678,"journal":{"name":"Cell calcium","volume":"124 ","pages":"Article 102957"},"PeriodicalIF":4.3000,"publicationDate":"2024-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Cell calcium","FirstCategoryId":"99","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0143416024001155","RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"CELL BIOLOGY","Score":null,"Total":0}
引用次数: 0

Abstract

TRP Vanilloid 1 (TRPV1) channel, one of the major members of the TRP family was discovered to play a critical role in pain sensation, particularly inflammatory pain, and is associated with hyperalgesia, an enhanced sensitivity to pain. A new study by Fan et al. Structural basis of TRPV1 inhibition by SAF312 and cholesterol” sheds new light on the mechanistic structural basis of TRPV1 inhibition by SAF312 (Libvatrep), a TRPV1 antagonist, currently in phase II clinical trials. They discover that the binding site of SAF312 in TRPV1 is in close vicinity and partially overlaps with the binding site of cholesterol and that removal of cholesterol interferes with the ability of SAF312 to suppress TRPV1 current.
查看原文
分享 分享
微信好友 朋友圈 QQ好友 复制链接
本刊更多论文
临床试验中的拮抗剂对 TRPV1 的抑制依赖于胆固醇的结合。
TRP Vanilloid 1(TRPV1)通道是 TRP 家族的主要成员之一,被发现在痛觉,尤其是炎症性疼痛中起着关键作用,并与痛觉减退(对疼痛的敏感性增强)有关。Fanet等人的一项新研究 "SAF312和胆固醇抑制TRPV1的结构基础 "揭示了TRPV1拮抗剂SAF312(Libvatrep)抑制TRPV1的机制结构基础。他们发现,SAF312 在 TRPV1 中的结合位点与胆固醇的结合位点非常接近并部分重叠,去除胆固醇会干扰 SAF312 抑制 TRPV1 电流的能力。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
求助全文
约1分钟内获得全文 去求助
来源期刊
Cell calcium
Cell calcium 生物-细胞生物学
CiteScore
8.70
自引率
5.00%
发文量
115
审稿时长
35 days
期刊介绍: Cell Calcium covers the field of calcium metabolism and signalling in living systems, from aspects including inorganic chemistry, physiology, molecular biology and pathology. Topic themes include: Roles of calcium in regulating cellular events such as apoptosis, necrosis and organelle remodelling Influence of calcium regulation in affecting health and disease outcomes
期刊最新文献
NAADP signaling: Master manipulation. Electrogenic and non-electrogenic ion antiporters participate in controling membrane potential. Commentary on: Li et al.; Ca2+ transients on the T cell surface trigger rapid integrin activation in a timescale of seconds. Nature Communications (2024) Distribution and calcium signaling function of somatostatin receptor subtypes in rat pituitary Calcium signals as regulators of ferroptosis in cancer
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
现在去查看 取消
×
提示
确定
0
微信
客服QQ
Book学术公众号 扫码关注我们
反馈
×
意见反馈
请填写您的意见或建议
请填写您的手机或邮箱
已复制链接
已复制链接
快去分享给好友吧!
我知道了
×
扫码分享
扫码分享
Book学术官方微信
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术
文献互助 智能选刊 最新文献 互助须知 联系我们:info@booksci.cn
Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。
Copyright © 2023 Book学术 All rights reserved.
ghs 京公网安备 11010802042870号 京ICP备2023020795号-1