Chemical modulation of Kv7 potassium channels. Issue 4 (14th January 2021)

• Record Type: Journal Article
• Authors: Borgini, Matteo; Mondal, Pravat; Liu, Ruiting; Wipf, Peter
• Is Part Of: RSC medicinal chemistry. Volume 12:Issue 4(2021)
• Page Start: 483
• Page End: 537
• Publication Date: 2021-01-14
• Subjects: Pharmaceutical chemistry -- Periodicals; 615.19005
• DOI: 10.1039/d0md00328j
• Languages: English
• ISSNs: 2632-8682

Abstract

Abstract : This review describes the synthetic and medicinal chemistry of small molecule modulators of the voltage-gated Kv7 (KCNQ) potassium channels and the available data of their biological and clinical properties. Abstract : The rising interest in Kv7 modulators originates from their ability to evoke fundamental electrophysiological perturbations in a tissue-specific manner. A large number of therapeutic applications are, in part, based on the clinical experience with two broad-spectrum Kv7 agonists, flupirtine and retigabine . Since precise molecular structures of human Kv7 channel subtypes in closed and open states have only very recently started to emerge, computational studies have traditionally been used to analyze binding modes and direct the development of more potent and selective Kv7 modulators with improved safety profiles. Herein, the synthetic and medicinal chemistry of small molecule modulators and the representative biological properties are summarized. Furthermore, new therapeutic applications supported by in vitro and in vivo assay data are suggested.