Ask about this productRelated genes to: KCNQ2 Blocking Peptide
- Gene:
- KCNQ2 NIH gene
- Name:
- potassium voltage-gated channel subfamily Q member 2
- Previous symbol:
- EBN, EBN1
- Synonyms:
- Kv7.2, ENB1, BFNC, KCNA11, HNSPC
- Chromosome:
- 20q13.33
- Locus Type:
- gene with protein product
- Date approved:
- 1998-01-12
- Date modifiied:
- 2016-02-04
Related products to: KCNQ2 Blocking Peptide
Related articles to: KCNQ2 Blocking Peptide
- - Source: PubMed
Publication date: 2026/05/25
Cheng XinyuWan ShuangyanJiang DexiangZhang HangyuHu BinChe TongChen YuanpengNan WeiweiZhou ZhuoXiao ChenxinZhong LingZhang YutingXiong BingHou PanpanZhang Jin - Voltage-gated potassium channel KCNQ1 (Kv7.1) plays a critical role in electrical excitability in the heart, gut, and brain. Together with the auxiliary subunit KCNE1, KCNQ1 generates a slow delayed rectifier current () that is essential for cardiac repolarization. Mutations and dysregulation of this channel are found in channelopathies leading to sudden death, long-QT syndrome, atrial fibrillation, epilepsy, deafness, diabetes, and neuropsychiatric disorders. Although KCNQ1 and related potassium channels are promising therapeutic targets, there are few potent, selective, and therapeutically safe inhibitors and activators available for these proteins. A virtual screening of 36,374 compounds was conducted against KCNQ1, followed by analyses that identified eight potential ligand candidates for experimental evaluation using human KCNQ1 coexpressed with KCNE1 in oocytes. Electrophysiological recordings showed that the benzodiazepine-based ligand Zinc13732787 was a potent inhibitor of the channel complex, without affecting KCNQ2/KCNQ3. Based on virtual screening and molecular docking, the 1-(3-chlorophenyl)-urea substituent on the benzodiazepine core is important for selective inhibition of KCNQ1/KCNE1, as further supported by structure-activity relationship and stereochemical exploration of Zinc13732787. Furthermore, low concentrations of Zinc13732787 reduced neurite outgrowth in human neuronal stem cells (NSCs), mirroring the phenotype observed in homozygous -knockout cells. Importantly, Zinc13732787 did not affect NSC proliferation, nor did it induce cytotoxicity. In homozygous -knockout NSCs, compound Zinc13732787 had no effect on neurite outgrowth, indicating high target specificity. These findings suggest that this compound is a valuable tool for investigating the physiological and pathological roles of KCNQ1 across various tissues. Additionally, it could be used as a precursor for novel antiarrhythmic agents as well as for epilepsy and neuropsychiatric conditions. - Source: PubMed
Publication date: 2026/05/21
Alam Kazi AsrafulMartí-Solans JosepSchall DorotheaKumar SumitIqbal Shahid MuhammadTeigen KnutBerkel SimoneMauceri DanielaHaug Bengt ErikLiin Sara ILynagh TimothyMartinez AuroraHaavik Jan - Focal epilepsy is a leading cause of neurological disability, with about one-third of patients failing to achieve seizure freedom despite numerous antiseizure medications (ASMs) are available. Most current therapies broadly modulate synaptic transmission, leading to dose-limiting cognitive, psychiatric, and systemic adverse effects. Kv7 (KCNQ) potassium channels, responsible for the neuronal M-current, represent a high-precision therapeutic target that regulates intrinsic excitability and provides a fundamental 'molecular brake' against pathological firing. - Source: PubMed
Publication date: 2026/05/19
Pelorosso CristianaBalestrini SimonaGuerrini Renzo - Genetic etiologies underlie a substantial proportion of pediatric dystonia, but whether treatment response to combined dopaminergic and anticholinergic therapy varies by genotype remains unknown. - Source: PubMed
Publication date: 2026/05/12
Zhou XiaolinLi YuLuo XiangyangHe ZhanwenLiu MujinLi Pinggan - Biological systems execute discrete, often irreversible actions - from DNA replication and cell-state transitions to Venus flytrap closure, vertebrate sex change, and human symbolic behavior - not as graded responses to single variables but as threshold-governed events emerging from the convergence of multiple necessary conditions. Here we formalize this convergence logic as the ARCH × Φ framework: a multiplicative threshold function in which Archetype (A, the conserved structural substrate), Drive (D, the energetic or hormonal activation), Context (C, the releasing stimulus or social cue), and Gating Field (Φ, a sterol-modulated permissiveness variable) must jointly exceed a system-specific commitment threshold θ. The multiplicative structure enforces a zero-term veto: suppression of any single component collapses execution regardless of the state of the other three. We trace the physical origin of Φ to the incorporation of sterols into eukaryotic membranes approximately 2.4 billion years ago, at the Great Oxidation Event, when oxygen-dependent sterol biosynthesis first separated stored electrochemical drive from discharge permissiveness - two quantities physically coupled in all pre-sterol membrane systems and independently tunable only with the arrival of the cholesterol ring structure. We propose that Φ is instantiated across three cholesterol-derived tiers: rapid modulation through accessible cholesterol pools and their oxysterol derivatives, intermediate modulation through neurosteroids synthesized via mitochondrial pathways, and lifetime-scale modulation through structural cholesterol deployment in myelin and perineuronal nets - all expressions of a single biophysical mechanism. We extend this account to two additional isoprenoid-based Φ systems: non-photochemical quenching (NPQ) in plant chloroplasts, where zeaxanthin and the PsbS protein constitute a zero-term veto gate for light-energy dissipation that is characterized to picosecond resolution, and insect holometabolous metamorphosis, where juvenile hormone functions as a Φ-suppressor and the dietary sterol auxotrophy of insects produces an environmentally gated Φ architecture distinct from the endogenous sterol synthesis of vertebrates. Monogenic Φ-lock disorders - exemplified by Niemann-Pick type C disease, in which disrupted intracellular cholesterol trafficking abolishes KCNQ2/3-dependent inhibitory gating - provide pathological proof-of-concept for the Φ-lock failure mode at the molecular level. The framework is formally equivalent to the h inactivation variable derived independently by Hodgkin and Huxley from squid axon voltage-clamp data in 1952, implying that Φ is not solely a theoretical construct but a measurable property of excitable membranes with a 2.4-billion-year evolutionary history. Explicit, falsifiable predictions are derived regarding perturbation-matrix experiments, CYP46A1 polymorphism effects on behavioral thresholds, the correlation of sterol enzyme diversity with behavioral plasticity rather than execution speed across taxa, dietary sterol auxotrophy and insect developmental plasticity, and τΦ acceleration as a route to increased biological output yield. - Source: PubMed
Publication date: 2026/05/08
Rahman TahirZorumski Charles F