Open AccessChemical modulation of Kv7 potassium channels
Author(s) -
Matteo Borgini,
Pravat Mondal,
Ruiting Liu,
Peter Wipf
Publication year - 2021
Publication title -
rsc medicinal chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.754
H-Index - 55
ISSN - 2632-8682
DOI - 10.1039/d0md00328j
Subject(s) - potassium channel , potassium , chemistry , voltage gated potassium channel , potassium channel blocker , modulation (music) , small molecule , voltage , biophysics , nanotechnology , biology , materials science , biochemistry , electrical engineering , physics , engineering , organic chemistry , acoustics
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.