Function and pharmacology of human Na+-activated K+ channels

人Na激活K通道的功能和药理学

• 批准号: 1943414
• 金额: --
• 依托单位: University of Leeds
• 依托单位国家: 英国
• 项目类别: Studentship
• 财政年份: 2017
• 资助国家: 英国
• 起止时间: 2017 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=studentship-1943414
• 关键词: Function; pharmacology; human; Na+; activated

Inherited and spontaneous gain-of-function mutations in the human KCNT1 gene, which encodes the SLACK Na+-activated K+ channel, have recently been linked to severe and drug-resistant epilepsies. Children suffering from these disorders have poor quality of life and many do not survive to adulthood. Inhibiting this channel with a potent and selective small molecule therapeutic is therefore a prioritised strategy for the treatment of these epilepsies. The SLACK channel is a poorly studied and understood potassium channel, with the Leeds group one of only a handful of laboratories with experience in studying its function, pharmacology, and effects of mutations. Underpinning fundamental research is required to understand (a) how exactly the epilepsy-related mutations affect both the structure and function of the channel, and (b) the mechanism by which known inhibitors and activators exert their effects.

编码SLACK Na+激活K+通道的人类KCNT1基因中的遗传性和自发性功能获得性突变最近与严重和耐药性癫痫有关。患有这些疾病的儿童生活质量很差，许多人不能活到成年。因此，用有效和选择性的小分子治疗剂抑制这一通道是治疗这些癫痫的优先策略。SLACK通道是一种研究和理解很少的钾通道，利兹小组是少数几个在研究其功能、药理学和突变效应方面有经验的实验室之一。需要进行基础研究来了解（a）癫痫相关突变如何确切地影响通道的结构和功能，以及（B）已知抑制剂和激活剂发挥作用的机制。

项目成果

Structure-based identification and characterisation of novel inhibitors of K Na 1.1 potassium channels, a stratified target for KCNT1 -related epilepsy

基于结构的 K Na 1.1 钾通道抑制剂（KCNT1 相关癫痫的分层靶标）的鉴定和表征

• DOI: 10.1101/779975
• 发表时间: 2019
• 作者: Cole B