ArtNr |
S2785-1000 |
Hersteller |
Selleckchem
|
CAS-Nr. |
944261-79-4 |
Menge |
1 g |
Kategorie |
|
Typ |
Inhibitors |
Specific against |
other |
ECLASS 10.1 |
32160490 |
ECLASS 11.0 |
32160490 |
UNSPSC |
12000000 |
Alias |
NaV1.8 channel;Sodium Channel |
Similar products |
A-803467 |
Lieferbar |
|
Administration |
Injected i.p. 30 minutes before behavioral testing |
Animal Models |
Male Sprague–Dawley rats subjected to spinal nerve ligation, sciatic nerve injury, capsaicin-induced secondary mechanical allodynia, or thermal hyperalgesia after intraplantar complete Freund's adjuvant injection, and male CD1 mice subjected to the abdominal constriction assay |
Chemical Name |
5-(4-chlorophenyl)-N-(3, 5-dimethoxyphenyl)furan-2-carboxamide |
Description |
A-803467 is a selective NaV1.8 channel blocker with IC50 of 8 nM. |
Dosages |
ca.100 mg/kg |
Features |
A-803467 is the first small-molecule blocker of sodium channels showing both high potency and significant subtype-selectivity among the sodium channel family. |
Formulation |
Dissolved in 5% DMSO/95% polyethylene glycol (PEG 400) |
IC50 |
8 nM [1], 8 nM [1], 8 nM [1], 8 nM [1], 8 nM [1], 8 nM [1] |
In vitro |
A-803467 potently blocks recombinant human or rat NaV1.8 channels with IC50 of 8 nM and 45 nM, respectively, at a holding potential of -40 mV. At a resting state, A-803467 also potently blocks human NaV1.8 channels with IC50 of 79 nM. A-803467 blocks tetrodotoxin-resistant (TTX-R) currents in rat dorsal root ganglion neurons in a concentration-dependent manner with IC50 of 140 nM, more potently compared with both mexiletine and lamotrigine with IC50 of >30 uM. A-803467 displays 300- to 1, 000-fold higher selectivity for hNaV1.8 over hNaV1.2, hNaV1.3, hNaV1.5, and hNaV1.7 channels with IC50 of 7.38 uM, 2.45 uM, 7.34 uM, and 6.74 uM, respectively. A-803467 shows no significant activity against other channels and receptors expressed in peripheral sensory neurons including TRPV1, P2X2/3, CaV2.2 and KCNQ2/3 channels with IC50 >10 uM. A-803467 also shows no or weak activity against a broad screening panel of cell-surface receptors, ion channels, and enzymes with IC50 of >2 uM. A-803467 at 0.3 uM but not 0.1 uM significantly inhibits the generation of spontaneous and electrically evoked action potentials. [1] |
In vivo |
Consistent with its effects on neuronal action potential electrogenesis in vitro, systemic administration of A-803467 (20 mg/kg, i.v.) to spinal nerve ligated rats, significantly reduces both spontaneous and von Frey hairevoked firing of spinal dorsal horn wide dynamic range neurons by 66% and 53%, respectively, compared with baseline levels. Administration of A-803467 also dose-dependently reduces mechanical allodynia in a variety of rat pain models including spinal nerve ligation (ED50 = 47 mg/kg, i.p.), sciatic nerve injury (ED50 = 85 mg/kg, i.p.), capsaicin-induced secondary mechanical allodynia (ED50 100 mg/kg, i.p.), and thermal hyperalgesia after intraplantar complete Freund's adjuvant injection (ED50 = 41 mg/kg, i.p.). A-803467 is inactive against formalin-induced nociception and acute thermal and postoperative pain, as well as in a chemotherapy-induced pain model (vincristine). [1] |
Kinase Assay |
Recombinant human sodium channels, HEK-293 cells expressing recombinant human NaV1.8 channels are grown in DMEM/high-glucose Dulbecco's modified, 10% FBS, 2 mM sodium pyruvate, and G418. For whole-cell voltage-clamp recordings, patch pipettes are pulled from borosilicate glass on a Flaming-Brown micropipette puller. Pipettes have a tip resistance of 0.8-2.5Momega with the internal solutions 135 mM CsF, 10 mM CsCl, 5 mM EGTA, 5 mM NaCl, 10 mM Hepes, pH to 7.3, with 5 M CsOH, and voltage offset is zeroed before seal formation. The external buffer consists of 132 mM NaCl, 5.4 mM KCl, 0.8 mM MgCl2, 1.8 mM CaCl2, 5 mM Glucose, and 10 mM Hepes-free acid, pH to 7.3, with 6 M NaOH. After establishment of a whole-cell recording, cellular capacitance is minimized by using the analog compensation available on the recording amplifier. Series resistance is 85% in all experiments, resulting in a final series resistance no greater than 0.75 Momega. Signals are low-pass filtered at 5-10 kHz, digitized at 20-50 kHz, and stored on a computer for later analysis. Voltage protocols are generated, and data acquisition and analysis are performed by using pCLAMP software. All experiments are performed at room temperature. Liquid junction potentials are <10mV and are not corrected. The concentration-response curve is generated after application of different concentrations of A-803467 and IC50 value of A-803467 is assessed at a holding potential of -40 mV. |
Molecular Weight (MW) |
357, 79 |
Picture ChemicalStructure Description |
A-803467 Chemical Structure |
Solubility (25C) |
DMSO 72 mg/mL, Water <1 mg/mL, Ethanol 11 mg/mL |
Storage |
2 years -20CPowder, 2 weeks4Cin DMSO, 2 months-80Cin DMSO |
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