| Name | A-803467 |
| Description | A-803467 is a selective NaV1.8 channel blocker. |
| Kinase Assay | Maize HD2, HD1-B, and HD1-A Enzyme Inhibition.: The enzyme liberats tritiated acetic acid from the substrate, which is quantified by scintillation counting. IC50 values are results of triple determinations. A 50 μL sample of maize enzyme (at 30 °C) is incubated (30 min) with 10 μL of total [3H]acetate-prelabeled chicken reticulocyte histones (2 mg/mL). Reaction is stopped by addition of 50 μL of 1 M HCl/0.4 M acetate and 800 μL of ethyl acetate. After centrifugation (1×104 g, 5 min), an aliquot of 600 μL of the upper phase is counted for radioactivity in 3 mL of liquid scintillation cocktail. MC1568 is tested at a starting concentration of 40 μM, and active substances are diluted further. NaB, VPA, TSA, SAHA, 85 TPX, HC-toxin, and tubacin are used as the reference compounds, and blank solvents are used as negative controls. |
| In vitro | A-803467 effectively reduced pain sensitivity in a dose-dependent manner in models including spinal nerve ligation (ED50 = 47 mg/kg, ip), sciatic nerve injury (ED50 = 85 mg/kg, ip), capsaicin-induced secondary mechanical allodynia (ED50 ≈ 100 mg/kg, intraperitoneally), and hyperalgesia following complete Freund's adjuvant injection into the plantar foot (ED50 = 41 mg/kg, intraperitoneally). Consistent with its effects on neuronal action potentials in vitro, systemic administration of A-803467 (20 mg/kg, iv) to rats with spinal nerve ligation significantly reduced both spontaneous and von Frey hair-induced responses in wide dynamic range neurons of the spinal cord dorsal horn by 66% and 53%, respectively. However, A-803467 was ineffective in models of harm induced by formalin, as well as acute thermal, postoperative pain, and pain caused by chemotherapy (vincristine). |
| In vivo | A-803467 selectively blocks tetrodotoxin-resistant (TTX-R) currents in rat dorsal root ganglion neurons in a concentration-dependent manner, with an IC50 of 140 nM, proving more effective than mexiletine and lamotrigine (IC50> 30 μM). It exhibits 300 to 1,000 times higher selectivity for hNaV1.8 over hNaV1.2, hNaV1.3, hNaV1.5, and hNaV1.7 channels, with respective IC50 values of 7.38 μM, 2.45 μM, 7.34 μM, and 6.74 μM. 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 an IC50 > 10 μM. It effectively blocks recombinant human or rat Nav1.8 channels at IC50s of 8 nM and 45 nM, maintained at a -40 mV potential. A-803467 also blocks human NaV1.8 channels in a resting state, with an IC50 of 79 nM. |
| Storage | Shipping with blue ice/Shipping at ambient temperature. |
| Solubility Information | Ethanol : 8.9 mg/mL (24.87 mM), Sonication is recommended.
10% DMSO+40% PEG300+5% Tween 80+45% Saline : 2 mg/mL (5.59 mM), Sonication is recommended.
DMSO : 65 mg/mL (181.67 mM), Sonication is recommended.
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| Keywords | tetrodotoxin-resistant | SodiumChannel | Sodium Channel | sodium | selective | potent | neuropathic | Nav1.8 | Na+ channels | Na(V1.8) channel | Na channels | Inhibitor | inhibit | inflammatory | channel | anti-nociception | A-803467 |
| Inhibitors Related | Phenytoin sodium | Procaine | Ranolazine dihydrochloride | Tetracaine hydrochloride | Lidocaine | Safinamide | Permethrin | Valproic Acid | L-Aspartic aicd sodium | Lidocaine hydrochloride | Mebeverine hydrochloride | Dibucaine |
| Related Compound Libraries | Highly Selective Inhibitor Library | Pain-Related Compound Library | Bioactive Compound Library | Membrane Protein-targeted Compound Library | Neuroprotective Compound Library | Inhibitor Library | Anti-Cardiovascular Disease Compound Library | NO PAINS Compound Library | Immunology/Inflammation Compound Library | Bioactive Compounds Library Max | Ion Channel Targeted Library | Anti-Cancer Active Compound Library |
United States
