{"title":"松弛钾通道小分子抑制剂作为儿童癫痫的潜在治疗药物。","authors":"Alshaima'a M Qunies, Kyle A Emmitte","doi":"10.4155/ppa-2022-0002","DOIUrl":null,"url":null,"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.","PeriodicalId":20011,"journal":{"name":"Pharmaceutical patent analyst","volume":"11 2","pages":"45-56"},"PeriodicalIF":1.8000,"publicationDate":"2022-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9260495/pdf/ppa-11-45.pdf","citationCount":"3","resultStr":"{\"title\":\"Small-molecule inhibitors of Slack potassium channels as potential therapeutics for childhood epilepsies.\",\"authors\":\"Alshaima'a M Qunies, Kyle A Emmitte\",\"doi\":\"10.4155/ppa-2022-0002\",\"DOIUrl\":null,\"url\":null,\"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.\",\"PeriodicalId\":20011,\"journal\":{\"name\":\"Pharmaceutical patent analyst\",\"volume\":\"11 2\",\"pages\":\"45-56\"},\"PeriodicalIF\":1.8000,\"publicationDate\":\"2022-03-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9260495/pdf/ppa-11-45.pdf\",\"citationCount\":\"3\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Pharmaceutical patent analyst\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.4155/ppa-2022-0002\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q3\",\"JCRName\":\"PHARMACOLOGY & PHARMACY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Pharmaceutical patent analyst","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.4155/ppa-2022-0002","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"PHARMACOLOGY & PHARMACY","Score":null,"Total":0}
Small-molecule inhibitors of Slack potassium channels as potential therapeutics for childhood epilepsies.
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.