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
Affiliations
Francesca Di Matteo
Department of Pharmacy, University of Salerno, Via G. Paolo II, 84084 Fisciano, Italy
Francesca Mancuso
Department of Chemical, Biological, Pharmaceutical and Environmental Sciences (CHIBIOFARAM), University of Messina, Viale F. Stagno d’Alcontres 31, 98166 Messina, Italy
Rita Turcio
Department of Pharmacy, University of Salerno, Via G. Paolo II, 84084 Fisciano, Italy
Tania Ciaglia
Department of Pharmacy, University of Salerno, Via G. Paolo II, 84084 Fisciano, Italy
Claudio Stagno
Department of Chemical, Biological, Pharmaceutical and Environmental Sciences (CHIBIOFARAM), University of Messina, Viale F. Stagno d’Alcontres 31, 98166 Messina, Italy
Carla Di Chio
Department of Chemical, Biological, Pharmaceutical and Environmental Sciences (CHIBIOFARAM), University of Messina, Viale F. Stagno d’Alcontres 31, 98166 Messina, Italy
Pietro Campiglia
Department of Pharmacy, University of Salerno, Via G. Paolo II, 84084 Fisciano, Italy
Alessia Bertamino
Department of Pharmacy, University of Salerno, Via G. Paolo II, 84084 Fisciano, Italy
Salvatore Vincenzo Giofrè
Department of Chemical, Biological, Pharmaceutical and Environmental Sciences (CHIBIOFARAM), University of Messina, Viale F. Stagno d’Alcontres 31, 98166 Messina, Italy
Carmine Ostacolo
Department of Pharmacy, University of Salerno, Via G. Paolo II, 84084 Fisciano, Italy
Nunzio Iraci
Department of Chemical, Biological, Pharmaceutical and Environmental Sciences (CHIBIOFARAM), University of Messina, Viale F. Stagno d’Alcontres 31, 98166 Messina, Italy
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.