Pharmacology and biophysics of the voltage-gated sodium channel Nav1.7: a therape

电压门控钠通道 Nav1.7 的药理学和生物物理学：一种疗法

• 批准号: 8145104
• 负责人: Seok-Yong Lee
• 金额: $ 235.5万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-09-30 至 2016-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8145104
• 关键词: Analgesics; Biophysics; Chemicals; Clinical; Consultations; Development; Disease; Electrophysiology (science); Future; Health; Medical; Pain; Patients; Pharmaceutical Preparations; Pharmacology; Physicians; Process; Proteins; Quality of life; Research; Research Proposals; Screening procedure; Sodium Channel; Symptoms; Syndrome; abstracting; chronic pain; drug development; innovation; insight; loss of function mutation; novel therapeutics; painful neuropathy; public health relevance; structural biology; tool; voltage

DESCRIPTION (Provided by the applicant) Abstract: Pain has been the most frequent reason for physician consultation, and chronic pain syndromes can severely undermine patients' qualities of life. Current analgesics are limited in that many patients with chronic pain syndromes or neuropathic pains do not respond to the drugs. Therefore there is a pressing need for new drug development along with a better understanding of the mechanism of the proteins that are the targets of these analgesics. Voltage-gated sodium channel subtype 1.7 is a newly emerging target for analgesic development. Using innovative approaches, I plan to characterize novel therapeutic regions of the voltage-gated sodium channel by a combination of tools, including chemical screening, structural biology, and electrophysiology. The proposed studies will provide new insights into future analgesic development as well as fundamental processes of voltage-gated sodium channels. Public Health Relevance: Pain is a major symptom in many medical conditions and chronic pain syndromes can severely reduce quality of life. There is a clear clinical need for new analgesics with a new mechanism of action. The voltage-gated sodium channel subtype 1.7 (Nav1.7) is a newly emerging target for analgesics, as patients with loss-of-function mutations in Nav1.7 do not feel pain. My research proposal is to study Nav1.7 by developing pharmacological tools and characterizing the mechanism of voltage sensing. My proposed research, if successful, will pave the way for the development of new analgesics and further our understanding of the mechanisms of voltage sensing in voltage-gated sodium channels in health and in disease.

描述（申请人提供） 摘要：疼痛一直是医师咨询的最常见原因，慢性疼痛综合症可能会严重破坏患者的生活品质。当前的镇痛药受到限制，因为许多患有慢性疼痛综合征或神经性疼痛的患者对药物没有反应。因此，对新药开发的紧迫需求以及对这些镇痛药靶标的机理的更好理解。电压门控钠通道亚型1.7是镇痛发育的新出现的靶标。我计划使用创新的方法来表征电压门控钠通道的新型治疗区域，包括化学筛选，结构生物学和电生理学。拟议的研究将为未来的镇痛发育以及电压门控钠通道的基本过程提供新的见解。 公共卫生相关性：在许多医疗状况中，疼痛是主要症状，慢性疼痛综合症可以严重降低生活质量。具有新的镇痛药具有新的作用机理。电压门控钠通道亚型1.7（NAV1.7）是新出现的镇痛药靶标，因为NAV1.7中功能丧失突变的患者不会感到疼痛。我的研究建议是通过开发药理学工具并表征电压传感机理来研究NAV1.7。我提出的研究，如果成功的话，将为发展新的镇痛药铺平道路，并进一步了解健康和疾病中电压门控钠通道中电压传感机理的理解。