A-803467

SKU: orb1306717

Description

A-803467

Research Area

Pharmacology & Drug Discovery

Key Properties

• CAS Number: 944261-79-4
• MW: 357.79
• Purity: 96.94%
• 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 IC50 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 int 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 o the spinal cord dorsal horn by 66% and 53%, respectively however, A-803467 was i effective 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.
• 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