Kv7.2/Kv7.3 activator-3
Kv7.2/Kv7.3 activator-3 (GRT-X) is an orally active Kv7.2/Kv7.3 and TSPO activator. Kv7.2/Kv7.3 activator-3 activates Kv7.2/Kv7.3, Kv7.4, and Kv7.5 with EC50 values of 0.37, 2.06, and 0.75 μM, respectively, and binds to TSPO with Ki values of 0.07 μM (rat membrane) and 4.60 μM (human U-118 MG cells). Kv7.2/Kv7.3 activator-3 prevents motor neuron degeneration in mice and humans conditioned by ALS/FTD astrocytes. Kv7.2/Kv7.3 activator-3 stimulates dorsal root ganglion axonal growth through TSPO and Kv7.2/3 activation. Kv7.2/Kv7.3 activator-3 has anti-epileptic effects in epileptic seizure models. Kv7.2/Kv7.3 activator-3 reduces pain hypersensitivity in patients with diabetic neuropathy, promotes neuronal survival and regeneration after cervical neuropathy in rats, and accelerates the recovery of normal function of sensory and motor neurons.
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- CAS No.: 1361107-81-4
- 화학식: C22H20F4N2O3
- 분자량:436.40
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보관:
Please store the product under the recommended conditions in the Certificate of Analysis.
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Biological Activity
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Chemical Information
- Protocol
- 순도&문서
- References
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Help & FAQs
Biological Activity
제품 설명
IC50 & Target
[1][2][3][4]|
KV7.2 0.37 μM (EC50) |
KV7.4 2.06 μM (EC50) |
KV7.5 0.75 μM (EC50) |
In Vitro
Kv7.2/Kv7.3 activator-3 (6.25-25 μM, 20 days) shows reduction in motoneurons (MNs) death in SCOCs[1].
Kv7.2/Kv7.3 activator-3 (0.1-10 μM, 4 days) does not reduce MNs survival up to 2.5 μM in rat primary spinal cord cultures (VSCNs)[1].
Kv7.2/Kv7.3 activator-3 (6.25-25 μM, 4 days) preserves MNs viability in SCOCs treated with human SOD1G93A-ACM/SOD1D90A-ACM/TDP43A90V-ACM[1].
Kv7.2/Kv7.3 activator-3 (1-2.5 μM, 4 days) rescues MNs death, reduces DCF counts in VSCNs treated with human SOD1G93A-ACM/SOD1D90A-ACM/TDP43A90V-ACM[1].
Kv7.2/Kv7.3 activator-3 (10 μM, 4 days) enhances the length and density of the neurite network, with a marked increase in AUC in embryonic C57BL6/J DRG[2].
Kv7.2/Kv7.3 activator-3 (10 μM, 8 days) maintains positive effect on axonal growth, increases AUCs in E13.5 DRG explants[2].
Kv7.2/Kv7.3 activator-3 (10 μM, 4 days) induces increased expression of genes involved in myelination, Schwann cell and neuronal development and differentiation, and axonal structure in E13.5 DRG explants [2].
Kv7.2/Kv7.3 activator-3 (10 μM, 4 days) has no effect on neurite outgrowth, but increases expression of genes associated with myelination and Schwann cell and neuronal development, but not genes involved in axonal structure in DIV4 embryonic TSPO-KO DRG explants[2].
Kv7.2/Kv7.3 activator-3 activates neuronal hKv7.2/3, hKv7.4, and hKv7.5 channels with a higher potency than retigabine in CHO-K1 cells[3].
Kv7.2/Kv7.3 activator-3 (10 μM) leads a potent and efficient hyperpolarization of the resting membrane potential (EC50 = 0.201 μM, maximal hyperpolarization: 13.2 mV) in cultured rat DRG neurons[4].
Kv7.2/Kv7.3 activator-3 (10 μM) binds to rat heart membranes with high and to human U-118 MG glioblastoma cells with moderate affinity in TSPO binding assays, enhances pregnenolone synthesis by cultured rat C6 glioma cells in TSPO functional assay[4].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only. Further protocols information, click here.
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Cell Line:SCOCs treated with SOD1G93A-ACM/SOD1D90A-ACM
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Concentration:6.25 μM, 12.5 μM,25 μM
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Incubation Time:4 days
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Result:Preserved MN viability.
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Cell Line:E13.5 DRG explants
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Concentration:10 μM
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Incubation Time:4 days
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Result:Induced a significant increase in the mRNA expression of TSPO, Kv7.2, Kv7.3, myelin-related genes (Mpz, Mbp and Plp), Dhh, Krox20 and CNPase, and increased the total mRNA expression levels of Tfap2α, Stmn2, Peripherin, Cad19, and Nfh genes.
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Cell Line:SPO-KO DRG explants
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Concentration:10 μM
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Incubation Time:4 days
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Result:Increased Kv7.2, Kv7.3, Mpz, Mbp, Plp, Dhh, CNPase Tfap2α, and Cad19 mRNA levels, and decreased Stmn2 expression.
Parmacokinetics
| Species | Dose | Route |
|---|---|---|
| Rat[1][2][3][4] | 10 mg/kg | p.o. |
In Vivo
Kv7.2/Kv7.3 activator-3 (0-10 mg/kg, p.o., once) prevents the occurrence of tonic epileptic seizures in Maximal electroshock seizure (MES) seizure male Wistar rats model[3].
Kv7.2/Kv7.3 activator-3 (0-3 mg/kg, p.o., once) increases seizure threshold in Electroconvulsive seizure (ECS) seizure male Wistar rats model[3].
Kv7.2/Kv7.3 activator-3 (0-100 mg/kg, p.o., once) increases latency to clonic seizures, decreases the incidence of tonic seizures in pentylenetetrazol (PTZ) seizure male Wistar rats model[3].
Kv7.2/Kv7.3 activator-3 (0-100 mg/kg, p.o., once) reduces incidence of tonic convulsions in PTZ seizure male SD rats model[3].
Kv7.2/Kv7.3 activator-3 (0-10 mg/kg, p.o., once) reduces the incidence of wild-running and clonic seizures, and prevents tonic seizures and mortality in male Rj:DBA/2 mice model[3].
Kv7.2/Kv7.3 activator-3 (0-100 mg/kg, p.o., once) prevents 6-Hz seizures in male NMRI mice model[3].
Kv7.2/Kv7.3 activator-3 (0.316-10 mg/kg, p.o., once) reduces hyperalgesia in Streptozotocin (STZ) (HY-13753)-induced chronic neuropathic pain (CNP) SD rats model[4].
Kv7.2/Kv7.3 activator-3 (5-10 mg/kg, p.o., once) promotes the survival and regeneration of neurons, accelerating the recovery of normal functions of sensory neurons and motor neuronsin severe cervical spinal nerve compression injury SD rats model[4].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:Male SD rat (200-230 g) model[3]
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Dosage:10 mg/kg
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Administration:p.o., once
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Result:Increased brain levels of neurosteroids, including 3α,5α-THP and 3α,5α-THDOC, increased 627% (pregnenolone), 107% (progesterone), 116% (5-α-dihydroprogesterone), 132% (3α,5α-THP), 4911% (deoxycorticosterone), 1333% (5α-deoxycorticosterone), and 1040% (3α,5α-THDOC), respectively in brain steroid levels.
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Animal Model:MES seizure male Wistar rats (200-230 g) model[3]
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Dosage:0 mg/kg, 1 mg/kg, 3 mg/kg, 10 mg/kg
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Administration:p.o., once
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Result:Prevented the occurrence of tonic epileptic seizures, with an ED50 of 3.7 mg/kg.
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Animal Model:ECS seizure male Wistar rats (200-230 g) model[3]
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Dosage:0 mg/kg, 0.3 mg/kg, 1 mg/kg, 3 mg/kg
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Administration:p.o., once
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Result:Increased seizure threshold.
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Animal Model:PTZ seizure male Wistar rats (200-230 g) model[3]
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Dosage:0 mg/kg, 10 mg/kg, 30 mg/kg, 100 mg/kg
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Administration:p.o., once
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Result:Increased latency to clonic seizures, decreased the incidence of PTZ-induced tonic seizures with ED50 of 37 mg/kg.
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Animal Model:PTZ seizure male SD rats (200-230 g) model[3]
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Dosage:0 mg/kg, 3 mg/kg, 10 mg/kg, 30 mg/kg, 100 mg/kg
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Administration:p.o., once
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Result:Reduced incidence of tonic convulsions.
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Animal Model:Male Rj:DBA/2 mice (12-15 g) model[3]
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Dosage:0 mg/kg, 1 mg/kg, 3 mg/kg, 10 mg/kg
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Administration:p.o., once
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Result:Reduced the incidence of wild-running and clonic seizures, and prevented tonic seizures and mortality.
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Animal Model:Male NMRI mice (21-25 g) model[3]
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Dosage:0 mg/kg, 10 mg/kg, 30 mg/kg, 100 mg/kg
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Administration:p.o., once
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Result:Prevented 6-Hz seizures with an ED50 of 13 mg/kg.
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Animal Model:STZ-induced (75 mg/kg) CNP SD rats[4]
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Dosage:0.316, 1.0, 10 mg/kg
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Administration:p.o., once
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Result:Reduced mechanical hyperalgesia.
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Animal Model:SD rats model[4]
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Dosage:10 mg/kg
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Administration:p.o., once
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Result:Increased the synthesis of anti-hyperalgesic neurosteroids.
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Animal Model:Severe cervical spinal nerve compression injury SD rats model[4]
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Dosage:5 mg/kg, 10 mg/kg
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Administration:p.o., once
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Result:Had neuroprotective and regenerative effects, accelerated and improved functional recovery after traumatic peripheral nerve injury.
Chemical Information
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CAS No. 1361107-81-4
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분자량 436.40
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화학식 C22H20F4N2O3
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SMILES
O=C(C1=C(C)C2=C(N(CCOC)C1=O)C=C(C(F)(F)F)C=C2)NCC3=CC=CC(F)=C3
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선적
Room temperature in continental US; may vary elsewhere.
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보관
Please store the product under the recommended conditions in the Certificate of Analysis.
Protocol
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Serum-Free B27/Neurobasal Neuronal Maintenance Culture
Serum-free B27/Neurobasal culture is a defined neuronal maintenance method designed to support dissociated primary neurons while limiting serum-driven glial expansion; the readout is sustained neuronal survival, neurite extension, neuronal marker expression, synapse formation, and, when measured, electrophysiological or calcium activity. B27/Neurobasal was optimized in embryonic rat hippocampal neurons, where B27 supported >60% survival after 4 days above 160 plated cells/mm2 and Neurobasal reduced glial growth to <0. 5% by immunocytochemistry; later studies extended the approach to cortex, striatum, substantia nigra, septum, cerebellum, and dentate gyrus neurons.
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Primary Dorsal Root Ganglion Sensory Neuron Culture
Primary dorsal root ganglion sensory neuron culture isolates DRG neuronal somata from rodent or human ganglia, dissociates tissue enzymatically and mechanically, and maintains post-mitotic sensory neurons in vitro for readouts such as neurite outgrowth, immunocytochemical marker expression, calcium imaging, electrophysiology, RNA/protein analysis, or neuropeptide release assays. The method reflects peripheral sensory neuron biology because DRG neurons are primary sensory neurons whose cell bodies reside in dorsal root ganglia and whose cultured dissociated cells can retain neuronal morphology, sensory-neuron marker expression, and stimulus-responsive properties depending on the downstream assay.
순도&문서
References
[1]. Masegosa VM, et al. Novel Dual Mechanism GRT-X Agonist Acting on Kv7 Potassium Channel/Translocator Protein Receptor Prevents Motoneuron Degeneration Following Exposure to Mouse and Human Amyotrophic Lateral Sclerosis/Frontotemporal Dementia Astrocyte-Conditioned Media. ACS Chem Neurosci. 2025 Aug 6;16(15):2887-2900 [Content Brief]
[2]. El Chemali L, et al. GRT-X Stimulates Dorsal Root Ganglia Axonal Growth in Culture via TSPO and Kv7.2/3 Potassium Channel Activation. Int J Mol Sci. 2024 Jul 3;25(13):7327. [Content Brief]
[3]. Bloms-Funke P, et al. The novel dual-mechanism Kv7 potassium channel/TSPO receptor activator GRT-X is more effective than the Kv7 channel opener retigabine in the 6-Hz refractory seizure mouse model. Neuropharmacology. 2022 Feb 1;203:108884. [Content Brief]
[4]. Bloms-Funke P et al.. A novel dual mode-of-action anti-hyperalgesic compound in rats which is neuroprotective and promotes neuroregeneration. Eur J Pharmacol. 2022 May 15;923:174935. [Content Brief]
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
Kv7.2/Kv7.3 activator-3 Related Classifications
HY-175340 Related Classifications
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