A-740003

SKU: orb1303893

Description

A-740003 is a potent and selective P2X7 receptor antagonist with IC50 values of 18 nM (rat) and 40 nM (human). It has demonstrated efficacy in reducing pain in rodent models of neuropathic and inflammatory pain and has also been shown to inhibit neuroblastoma tumor growth in vivo.

Research Area

Neuroscience, Pharmacology & Drug Discovery

Key Properties

• CAS Number: 861393-28-4
• MW: 474.55
• Purity: 99.68% (May vary between batches)
• Formula: C₂₆H₃₀N₆O₃
• SMILES: COc1ccc(CC(=O)NC(N\C(Nc2cccc3ncccc23)=N\C#N)C(C)(C)C)cc1OC
• Target: P2X Receptor
• Solubility: 10% DMSO+40% PEG300+5% Tween 80+45% Saline:1 mg/mL (2.11 mM);DMSO:9.5 mg/mL (20.02 mM)

Bioactivity

• Target IC50:
  P2X7 (human):40 nM|P2X7 (rat):18nM
• In Vivo:
  Administering A-740003 systemically results in a dose-dependent reduction of pain (antinociception) in rats, as evidenced in a spinal nerve ligation model (ED50=19 mg/kg i.p.), indicating its potency. Furthermore, A-740003 diminishes sensitivity to touch (tactile allodynia) in models of neuropathic pain, including chronic constriction of the sciatic nerve and vincristine-induced neuropathy. It also significantly lowers increased sensitivity to heat (thermal hyperalgesia) following the intraplantar introduction of carrageenan or complete Freund's adjuvant (ED50=38-54 mg/kg i.p.). However, A-740003 does not affect acute thermal pain in healthy rats and does not impair motor skills at doses that relieve pain.
• In Vitro:
  A-438079 and A-740003 (10 μM) effectively inhibit the prolonged phase of BzATP-induced responses and mitigate SE-induced TNF-α expression in dentate granule neurons while increasing SE-induced neuronal death. Compared to other antagonists, both compounds exhibit superior efficacy in inhibiting P2X7 receptor activation across various species, with heightened activity in rat and human compared to mouse P2X7 receptors. Specifically, A-740003 robustly inhibits agonist-induced IL-1β release (IC50=156 nM) and pore formation (IC50=92 nM) in differentiated human THP-1 cells.

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

A740003, A-740003, A 740003, inhibit, Inhibitor, P2X Receptor, P2X7 (Human), P2XRs, P2XReceptor, rat P2X7

Compound Identifiers

PubChem CID

72812793