Journal Article

KCNT1 Channel Blockers: A Medicinal Chemistry Perspective

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

2024

Overview

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.

• Publisher: MDPI AG,MDPI
• Subject: Amino acids / Animals / Anticonvulsants - chemistry / Anticonvulsants - pharmacology / Anticonvulsants - therapeutic use / Chemistry, Pharmaceutical - methods / Convulsions & seizures / Epilepsy / Epilepsy - drug therapy / Epilepsy - metabolism / epileptic encephalopathies / Etiology / Humans / KCNT1 blockers’ identification / KCNT1 potassium channel / Ligands / Lipids / medicinal chemistry campaigns / Mutation / Nerve Tissue Proteins - antagonists & inhibitors / Nerve Tissue Proteins - chemistry / Nerve Tissue Proteins - metabolism / Pharmaceutical sciences / Potassium / Potassium Channel Blockers - chemistry / Potassium Channel Blockers - pharmacology / Potassium Channel Blockers - therapeutic use / Potassium channels / Potassium Channels, Sodium-Activated / Potassium Channels, Tandem Pore Domain - antagonists & inhibitors / Potassium Channels, Tandem Pore Domain - chemistry / Potassium Channels, Tandem Pore Domain - metabolism / Potassium Channels, Voltage-Gated - antagonists & inhibitors / Potassium Channels, Voltage-Gated - metabolism / Review / Structure-Activity Relationship