Small-molecule inhibitors of Slack potassium channels as potential therapeutics for childhood epilepsies

Alshaima'A M. Qunies, Kyle A. Emmitte

Research output: Contribution to journalReview articlepeer-review

Abstract

Slack channels are sodium-Activated potassium channels that are encoded by the KCNT1 gene. Several KCNT1 gain of function mutations have been linked to malignant migrating partial seizures of infancy. Quinidine is an anti-Arrhythmic drug that functions as a moderately potent inhibitor of Slack channels; however, quinidine use is limited by its poor selectivity, safety and pharmacokinetic profile. Slack channels represent an interesting target for developing novel therapeutics for the treatment of malignant migrating partial seizures of infancy and other childhood epilepsies; thus, ongoing efforts are directed toward the discovery of small-molecules that inhibit Slack currents. This review summarizes patent applications published in 2020-2021 that describe the discovery of novel small-molecule Slack inhibitors.

Original languageEnglish
Pages (from-to)45-56
Number of pages12
JournalPharmaceutical Patent Analyst
Volume11
Issue number2
DOIs
StatePublished - Mar 2022

Keywords

  • 1,2,4-oxadiazole
  • 5-chlorindanyl
  • EIMFS
  • K1.1
  • KCNT1
  • MMPSI
  • Slack
  • Slo2.2

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