A-803467

SKU: orb1306717

Description

A-803467 is a potent and selective inhibitor of the voltage-gated sodium channel NaV1.8. This small molecule is a valuable research tool for investigating pain pathways in both in vitro electrophysiology studies and in vivo models of neuropathic and inflammatory pain.

Research Area

Pharmacology & Drug Discovery

Key Properties

• CAS Number: 944261-79-4
• MW: 357.79
• Purity: 98.00% (May vary between batches)
• Formula: C₁₉H₁₆ClNO₄
• SMILES: COc1cc(NC(=O)c2ccc(o2)-c2ccc(Cl)cc2)cc(OC)c1
• Target: Sodium Channel
• Solubility: Ethanol:8.9 mg/mL (24.87 mM);10% DMSO+40% PEG300+5% Tween 80+45% Saline:2 mg/mL (5.59 mM);DMSO:65 mg/mL (181.67 mM)

Bioactivity

• Target IC50:
  Nav1.8 channel:8 nM
• 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.
• 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).

Storage & Handling

• Storage: Powder: -20°C for 3 years | In solvent: -80°C for 1 year | Shipping with blue ice/Shipping at ambient temperature.
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Alternative Names

Inhibitor, inhibit, inflammatory, Na channels, Na(V1.8) channel, Na+ channels, Nav1.8, neuropathic, channel, anti-nociception, A-803467, A803467, A 803467, Sodium Channel, sodium, SodiumChannel, tetrodotoxin-resistant, selective, potent

Compound Identifiers

PubChem CID

16038374