2. Academic Validation
  3. Voltage-gated sodium channels: structures, functions, and molecular modeling

Voltage-gated sodium channels: structures, functions, and molecular modeling

  • Drug Discov Today. 2019 Jul;24(7):1389-1397. doi: 10.1016/j.drudis.2019.05.014.
Lei Xu 1,  Xiaoqin Ding 2,  Tianhu Wang 1,  Shanzhi Mou 3,  Huiyong Sun 4,  Tingjun Hou 5
Affiliations

Affiliations

  • 1 Institute of Bioinformatics and Medical Engineering, School of Electrical and Information Engineering, Jiangsu University of Technology, Changzhou 213001, China.
  • 2 Beijing Institute of Pharmaceutical Chemistry, Beijing 102205, China.
  • 3 School of Mathematics and Physics, Jiangsu University of Technology, Changzhou 213001, China.
  • 4 Department of Medicinal Chemistry, School of Pharmacy, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China. Electronic address: huiyongsun@cpu.edu.cn.
  • 5 College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China. Electronic address: tingjunhou@zju.edu.cn.
PMID: 31129313 DOI: 10.1016/j.drudis.2019.05.014
Abstract

Voltage-gated sodium channels (VGSCs), formed by 24 transmembrane segments arranged into four domains, have a key role in the initiation and propagation of electrical signaling in excitable cells. VGSCs are involved in a variety of diseases, including epilepsy, cardiac arrhythmias, and neuropathic pain, and therefore have been regarded as appealing therapeutic targets for the development of anticonvulsant, antiarrhythmic, and local anesthetic drugs. In this review, we discuss recent advances in understanding the structures and biological functions of VGSCs. In addition, we systematically summarize eight pharmacologically distinct ligand-binding sites in VGSCs and representative isoform-selective VGSC modulators in clinical trials. Finally, we review studies on molecular modeling and computer-aided drug design (CADD) for VGSCs to help understanding of biological processes involving VGSCs.

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