临床试验中的拮抗剂对 TRPV1 的抑制依赖于胆固醇的结合。

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

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引用次数: 0

摘要

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。

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

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.

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来源期刊

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