Kv7 Assays
Background of Kv7
Kv7, also designated as voltage-gated channel potassium subfamily Q, encoded 5 different members: Kv7.1-Kv7.5 channels. They may mediate M currents, thus representing ideal targets for therapeutic intervention in a wide variety of deceases and disorders, such as chronic inflammation, neuropathic pain, or epilepsy.
Fig.1. Structure Prediction of the Human Kv7.1. (Uniprot ID Q6PIL6; obtained from Alphafold)
Distributions and Functions of Kv7
Each of the five subunits of Kv7 may have a characteristic tissue distribution and function. Kv7.1 is mainly found in the heart and Kv7.4 is located in the cochlear area, both of which contribute to potassium transport. Kv7.2, Kv7.3, and Kv7.5 are widely expressed in ganglia and brain, and take part in controlling excitability.
Sub Units and Mechanisms of Kv7
The five subunits of the Kv7 subfamily may have a similar working mechanism.
| Units | Gene | Mechanism | Activator | Blocker |
| Kv7.1 | KCNQ1 |
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| Kv7.2 | KCNQ2 |
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| Kv7.3 | KCNQ3 |
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| Kv7.4 | KCNQ4 |
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| Kv7.5 | KCNQ5 |
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Assay List of Kv7 Channel
Creative Biolabs can provide a range of assays of Kv7 channels. You can choose the assay in the list or contact us for more information:
Kv7 Channels
Published Data
| Paper Title | Beyond retigabine: design, synthesis, and pharmacological characterization of a potent and chemically stable neuronal Kv7 channel activator with anticonvulsant activity |
| Journal | Journal of Medicinal Chemistry |
| Published | 2022 |
| Abstract | Epilepsy is a multiple and recurrent neurological disease. Although biological details of epilepsy have not yet been clarified, the unbalanced excitation and inhibition of the nervous system at different levels are currently recognized as a general principle of epileptic seizures which often involves abnormalities in cells, circuits, synapses, ions, membrane potentials, or large-scale neuronal networks in the nervous system. Voltage-gated neuronal potassium channels are key factors that determine neuronal excitability and neuronal input/output balance, and pharmacological activation of Kv7 channels is currently a feasible and reasonable method to improve epilepsy. In previous studies, several Kv7 channel activators have been developed, but most of them are difficult to pass the evaluation or show unexpected side effects in the clinical trial. In order to reduce side effects, increase Kv7 channel activation potency, and improve drug metabolic stability, several drug-like compounds were screened, synthesized, and evaluated in this research. |
| Result |
In this work, the researchers designed and synthesized a small library of conformationally constrained compounds, and conducted synthesis and in vitro/in vivo pharmacological evaluation of some of these compounds to explore their potential application in the treatment of epilepsy or other hyper-excitatory diseases. After the preliminary structural screening and evaluation, the pharmacological effects of compound 60 were confirmed. Fluorescence and electrophysiological analysis data show that compound 60 possesses better photochemical stability and Kv7 activation efficiency. Compound 60 exhibits higher brain distribution, longer half-life, and more effective anti-epileptic effect in the administration experiment of the acute epileptic seizure model in mice. Pharmacokinetic tests showed that compound 60 has better antiepileptic activity in vivo, and could be used as a Kv7-activating lead compound for the treatment of neuroexcitatory diseases. Overall, the researchers developed a novel Kv7-activating compound with favorable drug potency, neural channel selectivity, pharmacokinetic profile, and chemical stability, which can be used clinically in epilepsy or other hyperexcitatory neurological diseases.
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Fig.2. Functional characterization of the first series of Kv7 activator derivatives. (Musella, 2022)
Reference
- Musella, S.; et al. Beyond retigabine: design, synthesis, and pharmacological characterization of a potent and chemically stable neuronal Kv7 channel activator with anticonvulsant activity. Journal of Medicinal Chemistry. 2022, 65: 11340-11364.
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