Recent advances in small molecule Nav 1.7 inhibitors for cancer pain management.

Autor: Yu X; School of Pharmaceutical Engineering, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenhe District, Shenyang 110016, China., Zhao X; School of Pharmaceutical Engineering, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenhe District, Shenyang 110016, China., Li L; School of Pharmaceutical Engineering, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenhe District, Shenyang 110016, China., Huang Y; School of Pharmaceutical Engineering, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenhe District, Shenyang 110016, China., Cui C; School of Pharmaceutical Engineering, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenhe District, Shenyang 110016, China., Hu Q; School of Pharmaceutical Engineering, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenhe District, Shenyang 110016, China., Xu H; Yangtze River Pharmaceutical (Group) Co., Ltd., 1 South Yangtze River Road, Taizhou City, Jiangsu Province, 225321, China., Yin B; Yangtze River Pharmaceutical Group Jiangsu Haici Biological Pharmaceutical Co., Ltd., 8 Taizhen Road, Medical New & Hi-tech Industrial Development Zone, Taizhou City, Jiangsu Province, 225321, China., Chen X; Yangtze River Pharmaceutical Group Jiangsu Haici Biological Pharmaceutical Co., Ltd., 8 Taizhen Road, Medical New & Hi-tech Industrial Development Zone, Taizhou City, Jiangsu Province, 225321, China., Zhao D; Yangtze River Pharmaceutical Group Jiangsu Haici Biological Pharmaceutical Co., Ltd., 8 Taizhen Road, Medical New & Hi-tech Industrial Development Zone, Taizhou City, Jiangsu Province, 225321, China., Qiu Y; Yangtze River Pharmaceutical Group Jiangsu Haici Biological Pharmaceutical Co., Ltd., 8 Taizhen Road, Medical New & Hi-tech Industrial Development Zone, Taizhou City, Jiangsu Province, 225321, China., Hou Y; School of Pharmaceutical Engineering, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenhe District, Shenyang 110016, China. Electronic address: houyunlei901202@163.com.
Jazyk: angličtina
Zdroj: Bioorganic chemistry [Bioorg Chem] 2024 Sep; Vol. 150, pp. 107605. Date of Electronic Publication: 2024 Jun 29.
DOI: 10.1016/j.bioorg.2024.107605
Abstrakt: The dorsal root ganglion (DRG) is the primary neuron responsible for transmitting peripheral pain signals to the central nervous system and plays a crucial role in pain transduction. Modulation of DRG excitability is considered a viable approach for pain management. Neuronal excitability is intricately linked to the ion channels on the neurons. The small and medium-sized DRG neurons are chiefly engaged in pain conduction and have high levels of TTX-S sodium channels, with Nav1.7 accounting for approximately 80% of the current. Voltage-gated sodium channel (VGSC or Nav) blockers are vital targets for the management of central nervous system diseases, particularly chronic pain. VGSCs play a key role in controlling cellular excitability. Clinical research has shown that Nav1.7 plays a crucial role in pain sensation, and there is strong genetic evidence linking Nav1.7 and its encoding gene SCN9A gene to painful disorders in humans. Many studies have shown that Nav1.7 plays an important role in pain management. The role of Nav1.7 in pain signaling pathways makes it an attractive target for the potential development of new pain drugs. Meanwhile, understanding the architecture of Nav1.7 may help to develop the next generation of painkillers. This review provides updates on the recently reported molecular inhibitors targeting the Nav1.7 pathway, summarizes their structure-activity relationships (SARs), and discusses their therapeutic effects on painful diseases. Pharmaceutical chemists are working to improve the therapeutic index of Nav1.7 inhibitors, achieve better analgesic effects, and reduce side effects. We hope that this review will contribute to the development of novel Nav1.7 inhibitors as potential drugs.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024. Published by Elsevier Inc.)
Databáze: MEDLINE
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