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Purity: ≥98%
AF-353 (Ro-4; AF353) is a novel, highly potent, selective and orally bioavailable P2X3/P2X2/3 receptor antagonist with a pIC50 of 8.0 for both human and rat P2X3, and with a pIC50 of 7.3 for human P2X2/3. Antagonism of the P2X3 receptor is one of the potential therapeutic strategies for the management of neuropathic pain because P2X3 receptors are predominantly localized on small to medium diameter C- and Aδ-fiber primary afferent neurons, which are related to the pain-sensing system. Purinoceptors containing the P2X3 subunit (P2X3 homotrimeric and P2X2/3 heterotrimeric) are members of the P2X family of ion channels gated by ATP and may participate in primary afferent sensitization in a variety of pain-related diseases. The combination of a favourable pharmacokinetic profile with the antagonist potency and selectivity for P2X3 and P2X2/3 receptors suggests that AF-353 is an excellent in vivo tool compound for study of these channels in animal models and demonstrates the feasibility of identifying and optimizing molecules into potential clinical candidates, and, ultimately, into a novel class of therapeutics for the treatment of pain-related disorders.
ln Vitro |
AF-353 (Ro-4) exhibits great potency in suppressing intracellular calcium flux caused by α,β-meATP in cell lines that express recombinant rat and human P2X3 and human P2X2/3 channels [1]. With a p50 of 7.3, AF-353 (Ro-4) likewise inhibits human P2X2/3 channel activity, but with somewhat less potency [1].
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ln Vivo |
AF-353 (Ro-4) (10 mg/kg, 20 mg/kg; intravenously; for 4-6 hours) inhibits purinergic responses in both normal and spinal cord injured (SCI) rats [2]. It also shortens the systolic interval in normal rats but not in SCI rats [2]. Nevertheless, the frequency of non-voiding (NVC) is significantly reduced in SCI rats. AF-353 (Ro-4) does not impair oxygen levels or heart function [2].
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Animal Protocol |
Animal/Disease Models: Female SD (SD (Sprague-Dawley)) rats with SCI (250-300 g) [2]
Doses: 10 mg/kg, 20 mg/kg Route of Administration: intravenous (iv) (iv)injection; intravenous (iv) (iv)injection; intravenous (iv) (iv)injection. 90 minutes apart, lasting 4 hrs (hrs (hours)) to 6 hrs (hrs (hours)) Experimental Results: Purinergic responses were Dramatically diminished in both normal and SCI rats. |
References |
[1]. Gever JR, et al. AF-353, a novel, potent and orally bioavailable P2X3/P2X2/3 receptor antagonist. Br J Pharmacol. 2010 Jul;160(6):1387-1398.
[2]. Munoz A, et al. Modulation of bladder afferent signals in normal and spinal cord-injured rats by purinergic P2X3 and P2X2/3receptors. BJU Int. 2012 Oct;110(8 Pt B):E409-414. |
Molecular Formula |
C14H17N4O2I
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Molecular Weight |
400.21438
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CAS # |
865305-30-2
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SMILES |
NC1=NC=C(OC2=CC(I)=C(OC)C=C2C(C)C)C(N)=N1
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InChi Key |
AATPYXMXFBBKFO-UHFFFAOYSA-N
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InChi Code |
InChI=1S/C14H17IN4O2/c1-7(2)8-4-11(20-3)9(15)5-10(8)21-12-6-18-14(17)19-13(12)16/h4-7H,1-3H3,(H4,16,17,18,19)
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Chemical Name |
5-(5-iodo-4-methoxy-2-propan-2-ylphenoxy)pyrimidine-2,4-diamine
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Synonyms |
Ro-4; Ro 4; Ro4; AF353; AF-353; AF 353.
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Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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Solubility (In Vitro) |
DMSO : ~100 mg/mL (~249.87 mM)
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Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (6.25 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (6.25 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C,1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.5 mg/mL (6.25 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
1 mM | 2.4987 mL | 12.4934 mL | 24.9869 mL | |
5 mM | 0.4997 mL | 2.4987 mL | 4.9974 mL | |
10 mM | 0.2499 mL | 1.2493 mL | 2.4987 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration: mg/mL;
Method for preparing DMSO stock solution: mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation::Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O,mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.