A tamoxifen receptor within a voltage-gated sodium channel.
A tamoxifen receptor within a voltage-gated sodium channel.
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DOI：
10.1016/j.molcel.2020.12.048
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发表时间：
2021-03-18
期刊：
影响因子：
16
通讯作者：
Wallace BA
中科院分区：
文献类型：
--
作者：
Sula A;Hollingworth D;Ng LCT;Larmore M;DeCaen PG;Wallace BA
电压门控钠通道是许多镇痛和抗癫痫药物的靶点，其治疗机制和结合位点已得到充分表征。我们描述了 NavMs 电压门控钠通道内先前未识别的受体位点的识别。他莫昔芬是一种雌激素受体调节剂，其初级和次级代谢产物结合在通道的细胞内出口处，该位点不同于先前表征的其他钠通道药物位点。这些化合物以相似的效力抑制 NavM 和人类钠通道，并通过延迟通道从失活状态恢复来防止钠电导。因此，这项研究不仅描述了可用于开发治疗钠离子通道病的新药的位点的结构和药理学，而且还可能对这种广泛使用的治疗药物的脱靶健康影响产生重要影响。他莫昔芬/电压门控钠通道复合物的结构和功能 他莫昔芬与钠通道中先前未识别的药物结合位点结合 钠通道他莫昔芬结合袋与雌激素受体具有相同的特征 X射线晶体学和电生理学揭示了药物他莫昔芬（及其代谢衍生物）与电压门控钠通道相互作用的本质。
Voltage-gated sodium channels are targets for many analgesic and antiepileptic drugs whose therapeutic mechanisms and binding sites have been well characterized. We describe the identification of a previously unidentified receptor site within the NavMs voltage-gated sodium channel. Tamoxifen, an estrogen receptor modulator, and its primary and secondary metabolic products bind at the intracellular exit of the channel, which is a site that is distinct from other previously characterized sodium channel drug sites. These compounds inhibit NavMs and human sodium channels with similar potencies and prevent sodium conductance by delaying channel recovery from the inactivated state. This study therefore not only describes the structure and pharmacology of a site that could be leveraged for the development of new drugs for the treatment of sodium channelopathies but may also have important implications for off-target health effects of this widely used therapeutic drug. Structure and function of tamoxifen/voltage-gated sodium channel complexes Tamoxifen binds to a previously unidentified drug binding site in sodium channels Sodium channel tamoxifen binding pocket shares features with the estrogen receptor X-ray crystallography and electrophysiology reveal the nature of the interactions of the drug tamoxifen (and its metabolic derivatives) with voltage-gated sodium channels.
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DOI：
10.1152/ajpheart.00686.2002
发表时间：
2003-08-01
影响因子：
4.8
作者：
He, JY;Kargacin, ME;Ward, CA
通讯作者：
Ward, CA
影响因子：
8.8
作者：
LIEN, EA;WESTER, K;UELAND, PM
通讯作者：
UELAND, PM
调节癌症电压门控通道表达：激素，生长因子和自身调节。
DOI：
10.1098/rstb.2013.0105
发表时间：
2014-03-19
期刊：
Philosophical transactions of the Royal Society of London. Series B, Biological sciences
影响因子：
--
作者：
Fraser SP;Ozerlat-Gunduz I;Brackenbury WJ;Fitzgerald EM;Campbell TM;Coombes RC;Djamgoz MB
通讯作者：
Djamgoz MB
影响因子：
14.9
作者：
Chiu, J;March, PE;Tillett, D
通讯作者：
Tillett, D
影响因子：
2.6
作者：
Klein DJ;Thorn CF;Desta Z;Flockhart DA;Altman RB;Klein TE
通讯作者：
Klein TE