A-317491

Catalog No.S8519

For research use only.

A-317491 is a novel potent and selective non-nucleotide antagonist of P2X3 and P2X2/3 receptors with Ki values of 22 nM and 9 nM for human P2X3 and P2X2/3 receptors.

A-317491 Chemical Structure

CAS No. 475205-49-3

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Biological Activity

Description A-317491 is a novel potent and selective non-nucleotide antagonist of P2X3 and P2X2/3 receptors with Ki values of 22 nM and 9 nM for human P2X3 and P2X2/3 receptors.
Targets
Human P2X2/3 [1]
(Cell-free assay)
Human P2X3 [1]
(Cell-free assay)
Rat P2X3 [1]
(Cell-free assay)
Rat P2X2/3 [1]
(Cell-free assay)
9 nM(Ki) 22 nM(Ki) 22 nM(Ki) 92 nM(Ki)
In vitro

A-317491 potently blocks recombinant human and rat P2X3 and P2X2/3 receptor-mediated calcium flux (Ki = 22-92 nM) and is highly selective (IC50 >10 μM) over other P2 receptors and other neurotransmitter receptors, ion channels, and enzymes. A-317491 does not undergo any detectable metabolism (oxidation or glucuronidation) in in vitro assays using human and rat liver microsomes[1].

In vivo A-317491 dose-dependently (ED50 = 30 μmol/kg s.c.) reduces complete Freund's adjuvant-induced thermal hyperalgesia in the rat. A-317491 is most potent (ED50 = 10-15 μmol/kg s.c.) in attenuating both thermal hyperalgesia and mechanical allodynia after chronic nerve constriction injury. Although active in chronic pain models, A-317491 is ineffective (ED50 >100 μmol/kg s.c.) in reducing nociception in animal models of acute pain, postoperative pain, and visceral pain. Preliminary pharmacokinetic studies in rats indicate that 10 μmol/kg A-317491 had high (≈80%) systemic bioavailability after s.c. dosing (estimated plasma concentration = 15 μg/ml, >99% protein bound) and a half-life in plasma of 11 h[1]. A-317491 is effective in reducing pain associated behavior in several animal models of inflammatory and neuropathic pain when administered systemically. A-317491 does not significantly penetrate into the CNS[2].

Protocol (from reference)

Animal Research:

[2]

  • Animal Models: male Sprague-Dawley rats
  • Dosages: 3, 10 and 30 mg/kg
  • Administration: s.c.

Solubility (25°C)

In vitro

Chemical Information

Molecular Weight 565.57
Formula

C33H27NO8

CAS No. 475205-49-3
Storage 3 years -20°C powder
2 years -80°C in solvent
Smiles C1CC(C2=CC=CC=C2C1)N(CC3=CC(=CC=C3)OC4=CC=CC=C4)C(=O)C5=CC(=C(C=C5C(=O)O)C(=O)O)C(=O)O

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Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O, mix and clarify.

Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.

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Tech Support

Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

Handling Instructions

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