Ask about this productRelated genes to: Kcnt1 Blocking Peptide
- Gene:
- KCNT1 NIH gene
- Name:
- potassium sodium-activated channel subfamily T member 1
- Previous symbol:
- -
- Synonyms:
- KCa4.1, KIAA1422, SLACK, Slo2.2
- Chromosome:
- 9q34.3
- Locus Type:
- gene with protein product
- Date approved:
- 2002-07-10
- Date modifiied:
- 2016-04-25
Related products to: Kcnt1 Blocking Peptide
Related articles to: Kcnt1 Blocking Peptide
- KCNT1 channels are important targets in a variety of conditions, especially childhood epilepsies associated with activating mutations. Growing interest in this target has driven the discovery of KCNT1 channel modulators to serve as probes and leads for the development of novel therapeutics. Early pharmacological modulators such as quinidine, bepridil, and clofilium found through drug repurposing were generally limited by poor selectivity, low potency, and safety concerns, restricting their clinical potential. Structure-guided virtual screening, high-throughput screening, and systematic optimization have identified a suite of new KCNT1 modulators with more favorable pharmacological properties than existing probes identified through drug repurposing. This review provides an overview of the peer-reviewed literature describing chemotypes with structural features that enhance potency and selectivity compared to earlier KCNT1 modulators. Also discussed are structure-activity relationship (SAR) studies that have enabled the rational optimization of molecules to enhance overall drug-like properties. Together, these insights provide a foundation for the rational design of next generation KCNT1-targeted therapies. Progress in this field has been tremendous, and the chemical diversity of small molecule KCNT1 inhibitors has grown rapidly. While KCNT1 activators are rarer, progress has been made in this area as well. - Source: PubMed
Publication date: 2026/05/06
Peprah Paul KEmmitte Kyle A - Severe drug-resistant childhood epilepsy is caused by KCNT1 gain-of-function genetic variants, resulting in increased K1.1 channel activity. KCNT1-associated epilepsy is thought to affect around 1 in 300,000 births worldwide. Current treatment for KCNT1 epilepsy only provides mild symptomatic relief and uses a cocktail of experimental medications which must be personalised for the individual and are often poorly tolerated. Critically, with many patients, no therapeutic benefit is achieved. We sought to address this by using large-scale virtual screening to accelerate the development of a molecule which binds directly to KCNT1 to supress overactivity. We purchased a total of 71 compounds and using a combination of fluorescent thallium flux assays and patch clamp electrophysiology, identified a series of eight structurally diverse, novel inhibitors of the K1.1 channel with potency in the low micromolar range. These provide potential starting points for further development of drugs to treat KCNT1-associated epilepsy. - Source: PubMed
Publication date: 2026/04/25
Caseley Emily ASimmons Katie JCole Bethan AFlynn Alex JMuench Stephen PLippiat Jonathan D - Dysfunction of the sodium-activated potassium channel K1.1 (encoded by KCNT1) is associated with a severe neurodevelopmental condition characterized by frequent seizures (up to hundreds per day), treatment resistance, and increased mortality during childhood. Yet, recent progress with an RNA therapy targeting KCNT1 offers clinical promise. We characterize the early developmental onset of K1.1 channels in prenatal and neonatal brain tissue, establishing a timeline for pathophysiology and a window for therapeutic intervention. Using patch-clamp electrophysiology, we observe functional prenatal K1.1 conductance that is developmentally regulated. In excitatory and inhibitory neurons derived from a child's induced pluripotent stem cells with a KCNT1 pathogenic variant (p.R474H), we detect gain-of-function K currents. We use an antisense oligonucleotide RNA therapy developed for two individuals with the p.R474H variant-which results in dramatic reductions in seizure occurrence and severity-to profile cellular neurophysiology in patient-derived excitatory and inhibitory neurons. We observe a knockdown of p.R474H gain-of-function K currents, resulting in a stimulation-dependent change in spiking output in patient-derived induced excitatory and inhibitory neurons. In mid-gestation primary human neurons, ASO knockdown suppresses current-evoked firing, suggesting a potential early therapeutic target before the onset of infantile encephalopathy. - Source: PubMed
Publication date: 2026/04/29
Golinski Sean RSoriano KarlaBriegel Alex CBurke Madeline CTang ShengCarvill Gemma LSherrill EmmaLentucci ClaudiaYu Timothy WNakayama TojoHu RuilongSmith Richard S - BACKGROUND Potassium sodium-activated channel subfamily T member 1 (KCNT1)-related developmental and epileptic encephalopathy (DEE) is a rare and serious neurological condition attributed to damaging alterations in the KCNT1 gene, which encodes a sodium-activated potassium channel involved in neuronal excitability. It typically manifests in infancy with drug-resistant seizures, developmental delay, and hypotonia. Diagnosis is determined using whole-exome sequencing. Although KCNT1-related epilepsy is considered as a rare disorder, reporting such individual cases may help broaden the clinical and genetic spectrum of this condition. This report describes a Bahraini girl who first presented with symptoms at 2 weeks of age and at the time of this report was 4 years old, with developmental delay and epilepsy of infancy with migrating focal seizures (EIMFS), and early-onset DEE, associated with KCNT1 gene mutation. CASE REPORT A previously healthy term female baby presented at 2 weeks of age with focal seizures that progressed to intractable migrating focal epilepsy. At 4 months, she developed developmental regression, losing the ability to roll over, social-smile, and make eye contact. Neurological examination revealed central hypotonia with poor visual interaction. Electroencephalogram (EEG) showed multifocal epileptiform discharges with migrating seizure activity. Brain magnetic resonance imaging (MRI) and metabolic investigations were normal. Whole-exome sequencing identified a heterozygous KCNT1 variant, confirming developmental and epileptic encephalopathy type 14 (DEE14). CONCLUSIONS This case highlights the importance of timely genetic testing in infants showing severe epilepsy and developmental issues. To better understand the phenotypic variability and clinical course of KCNT1-related epileptic encephalopathy, more case reports are required. Identifying a KCNT1 mutation provides diagnostic clarity, supports precise prognosis and genetic counseling, and may help evaluate future targeted treatments. - Source: PubMed
Publication date: 2026/04/28
AlHadi Noora EbrahimAlbuainain Hessa MohammedJadah Raafat Hammad - Pathogenic variants in KCNT1, encoding the sodium-activated potassium channel K1.1 (Slack), cause severe developmental and epileptic encephalopathies marked by early-onset, treatment-resistant seizures and profound neurodevelopmental impairment. While clinical and electrophysiological features are well described, systematic caregiver-reported data on treatment effectiveness and family impact are limited. - Source: PubMed
Publication date: 2026/04/24
Bryan Brad AFaria VictorEsposito KaitlynBoyce DaniellePoliquin SarahTerry IanWright MeganAbuhl AmandaRosenberg AllisonBearden DavidWest JustinDrislane Sarah