Molecules (Jun 2024)

KCNT1 Channel Blockers: A Medicinal Chemistry Perspective

  • Francesca Di Matteo,
  • Francesca Mancuso,
  • Rita Turcio,
  • Tania Ciaglia,
  • Claudio Stagno,
  • Carla Di Chio,
  • Pietro Campiglia,
  • Alessia Bertamino,
  • Salvatore Vincenzo Giofrè,
  • Carmine Ostacolo,
  • Nunzio Iraci

DOI
https://doi.org/10.3390/molecules29122940
Journal volume & issue
Vol. 29, no. 12
p. 2940

Abstract

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Potassium channels have recently emerged as suitable target for the treatment of epileptic diseases. Among potassium channels, KCNT1 channels are the most widely characterized as responsible for several epileptic and developmental encephalopathies. Nevertheless, the medicinal chemistry of KCNT1 blockers is underdeveloped so far. In the present review, we describe and analyse the papers addressing the issue of KCNT1 blockers’ development and identification, also evidencing the pros and the cons of the scientific approaches therein described. After a short introduction describing the epileptic diseases and the structure–function of potassium channels, we provide an extensive overview of the chemotypes described so far as KCNT1 blockers, and the scientific approaches used for their identification.

Keywords