Brandwine-Shemmer Tal, Minke Baruch, Levitan Irena
Department of Medical Neurobiology, Institute for Medical Research Israel-Canada (IMRIC), Edmond and Lily Safra Center for Brain Sciences (ELSC), Faculty of Medicine, The Hebrew University, Jerusalem, Israel.
Department of Medical Neurobiology, Institute for Medical Research Israel-Canada (IMRIC), Edmond and Lily Safra Center for Brain Sciences (ELSC), Faculty of Medicine, The Hebrew University, Jerusalem, Israel.
Cell Calcium. 2024 Dec;124:102957. doi: 10.1016/j.ceca.2024.102957. Epub 2024 Sep 25.
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 Fanet 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.
瞬时受体电位香草酸亚型1（TRPV1）通道是瞬时受体电位（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关键作用，并且与痛觉过敏（对疼痛的敏感性增强）相关。范等人发表的一项新研究“SAF312和胆固醇对TRPV1抑制作用的结构基础”，为目前正处于II期临床试验阶段的TRPV1拮抗剂SAF312（利布瓦特雷）抑制TRPV1的机制结构基础提供了新的线索。他们发现SAF312在TRPV1中的结合位点与胆固醇的结合位点相邻且部分重叠，并且去除胆固醇会干扰SAF312抑制TRPV1电流的能力。
