| Size | Price | Stock | Qty |
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| 500mg |
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| 1g |
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Purity: ≥98%
Proxyphylline is a derivative of methylxanthine that is clinically used as a cardiac stimulant, a vasodilator and a bronchodilator. Proxyphylline acts by specifically opposing A2 adenosine receptors (Ki = 850 µM for platelets) in contrast to A1 adenosine receptors (Ki of 82 nM for the bovine brain). Vasodilatory and cardiac stimulatory effects have been observed with proxyphylline. It causes a clear positive inotropic effect along with an increase in coronary flow. Half-maximum relaxation of tracheal smooth muscle is achieved with 100 μg/mL of proxyphylline, which suppresses tracheal PDE-activity.
| Targets |
A1 adenosine receptor
cAMP-phosphodiesterase (PDE) (IC50 ≈ 40 μg/ml) [2] cAMP phosphodiesterase (human lung tissue) (Ki = 0.06–0.7 mmol/L at low cAMP concentrations; Ki = 1.0 mmol/L at high cAMP concentrations) [4] cGMP phosphodiesterase (human lung tissue) (Ki = 0.06–0.7 mmol/L at low/high cGMP concentrations) [4] Coronary circulation/heart [1] Tracheal smooth muscle (half-maximum relaxation concentration = 100 μg/ml) [2] |
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| ln Vitro |
In vitro activity: Proxyphylline has demonstrated heart-stimulating and vasodilatory effects. Proxyphylline has a clear positive inotropic effect and increases coronary flow[1]. Half-maximum relaxation of the smooth muscle in the trachea is achieved at 100 μg/mL of proxyphylline, which suppresses tracheal PDE-activity[2]. 1. Proxyphylline inhibited tracheal cAMP-phosphodiesterase (PDE) activity in guinea-pig tracheal preparations with an IC50 of approximately 40 μg/ml (comparable to theophylline; diprophylline was ~5 times less effective); it induced half-maximum relaxation of guinea-pig tracheal smooth muscle at 100 μg/ml (higher than theophylline [25 μg/ml] and lower than diprophylline [250 μg/ml]); it increased cAMP levels in tracheal smooth muscle to a lesser extent than theophylline (diprophylline was almost ineffective); combined with theophylline and diprophylline (Neobiphyllin), it produced overadditive synergism in tracheal smooth muscle relaxation (the potentiated effect was not associated with increased cAMP levels); it had a positive inotropic effect in guinea-pig atria (unlike diprophylline with almost no effect). [2] 2. Proxyphylline inhibited cAMP and cGMP hydrolysis in human lung tissue; its apparent inhibition constant (Ki) was 0.06–0.7 mmol/L at low cAMP concentrations and low/high cGMP concentrations, and 1.0 mmol/L at high cAMP concentrations (1.2–1.7 times higher than theophylline); its main metabolite 1-methyl-7-(beta-hydroxypropyl)xanthine was a slightly weaker inhibitor than proxyphylline (theophylline metabolite 3-methylxanthine was relatively weaker than its parent drug). [4] |
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| ln Vivo |
Proxyphylline demonstrates bronchodilatory action[3]. In human lung tissue, proxyphylline inhibits the hydrolysis of cAMP and cGMP. Proxyphylline's apparent inhibition constant is 1.0 mM at high cAMP concentrations and 0.06–0.7 mM at low cAMP concentrations[3].
1. In a double-blind cross-over study with 8 adult asthmatics, oral sustained-release proxyphylline (900 mg, Neofyllin retard) administered twice daily for 6 days significantly reduced the number of bronchodilatory aerosol dosages used (139 dosages vs 236 dosages in placebo period, p < 0.05); the reduction was statistically significant compared with placebo, while theophylline (250 mg microcrystalline, Nuelin, 4 times daily for 6 days) showed a non-significant reduction (165 dosages vs placebo); subjective side-effects occurred significantly less often during proxyphylline treatment than during theophylline treatment (p < 0.05); intravenous infusion of proxyphylline (1400 mg) and aminophylline (400 mg) confirmed the potency difference in lung function changes (proxyphylline had lower potency than theophylline/aminophylline). [3] |
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| Enzyme Assay |
1. Tracheal PDE activity assay: Guinea-pig tracheal preparations were used to isolate cAMP-phosphodiesterase (PDE); the enzyme activity was measured in the presence of different concentrations of proxyphylline, theophylline, and diprophylline; the IC50 value for proxyphylline-mediated PDE inhibition was calculated (≈40 μg/ml) by quantifying enzyme activity reduction relative to control; the effect of drug combinations on PDE activity was also assessed (no significant change in cAMP-increasing effect at lower doses). [2]
2. Human lung cyclic nucleotide PDE inhibition assay: Human lung tissue was used to prepare cyclic nucleotide phosphodiesterase extracts; the hydrolysis of cAMP and cGMP was measured in the presence of proxyphylline, its metabolite 1-methyl-7-(beta-hydroxypropyl)xanthine, theophylline, and its metabolite 3-methylxanthine at different substrate concentrations (low/high cAMP/cGMP); the apparent inhibition constants (Ki) were calculated for each drug/metabolite to compare their inhibitory potency. [4] |
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| Cell Assay |
1. Tracheal smooth muscle relaxation assay: Guinea-pig tracheal smooth muscle preparations were isolated and exposed to proxyphylline, theophylline, and diprophylline at different concentrations; the muscle tone was measured to determine the half-maximum relaxation concentration (100 μg/ml for proxyphylline); the effect of drug combinations (theophylline + diprophylline + proxyphylline) on muscle relaxation was evaluated, and overadditive synergism was confirmed by comparing the relaxation effect of combinations with single drugs; cAMP levels in tracheal smooth muscle were quantified after drug treatment to analyze the correlation between cAMP levels and relaxation effect. [2]
2. Guinea-pig atrial contractile force assay: Isolated guinea-pig atrial preparations were treated with proxyphylline, theophylline, and diprophylline; the contractile force was measured to assess the positive inotropic effect (proxyphylline showed positive inotropy, while diprophylline had almost no effect). [2] |
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| Animal Protocol |
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| References |
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| Additional Infomation |
Proxyphylline is an oxopurine drug. It is a methylxanthine derivative of Proxyphylline. Proxyphylline relaxes smooth muscle, especially bronchial smooth muscle. This xanthine likely works by inhibiting cAMP or cGMP phosphodiesterase, thereby increasing the levels of the intracellular second messengers cAMP or cGMP. Other mechanisms of action include antagonizing adenosine activity in CD4 lymphocytes and promoting the release of mediators from mast cells, thereby reducing lung sensitivity to allergens and other inflammatory substances. Proxyphylline also acts as a central nervous system stimulant and has positive chronotropic and positive inotropic effects on the heart.
1. Prophylline is a methylxanthine derivative with bronchodilatory effects; its mechanism of bronchodilatory smooth muscle relaxation is related to cAMP-PDE inhibition and positive inotropic effects (unlike diphylline, the relaxation mechanism of diphylline is not related to cAMP); the superadditive synergistic effect among prophylline, Proxyphylline and diphylline (neo-diphylline) explains its good anti-asthmatic effect. [2] 2. Prophylline is less effective than Proxyphylline in inhibiting human pulmonary cyclic nucleotide phosphodiesterase (Ki value is 1.2-1.7 times higher than Proxyphylline), which is consistent with clinical findings that Proxyphylline is about twice as effective as prophylline; its metabolites have weaker inhibitory activity, but are relatively more effective than Proxyphylline metabolites. [4] 3. Sustained-release prophylline (neo-diphylline sustained-release tablets) is an oral preparation for the treatment of asthma. Compared with Proxyphylline, it is better tolerated (fewer side effects) and has a significant bronchodilatory effect, which can reduce the need for emergency bronchodilators. [3] 4. Sesquiterpenes hydrochloride can be used in combination with sweet osmanthus extract and rutin (tea tree extract) to study their effects on the heart and coronary circulation. [1] |
| Molecular Formula |
C10H14N4O3
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| Molecular Weight |
238.25
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| Exact Mass |
238.107
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| Elemental Analysis |
C, 50.41; H, 5.92; N, 23.52; O, 20.15
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| CAS # |
603-00-9
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| Related CAS # |
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| PubChem CID |
4977
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| Appearance |
White to off-white solid powder
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| Density |
1.46 g/cm3
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| Boiling Point |
487.2ºC
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| Melting Point |
134-136ºC
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| Flash Point |
248.5ºC
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| Index of Refraction |
1.664
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| LogP |
-0.8
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
4
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| Rotatable Bond Count |
2
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| Heavy Atom Count |
17
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| Complexity |
348
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| Defined Atom Stereocenter Count |
0
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| SMILES |
O([H])C([H])(C([H])([H])[H])C([H])([H])N1C([H])=NC2=C1C(N(C([H])([H])[H])C(N2C([H])([H])[H])=O)=O
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| InChi Key |
KYHQZNGJUGFTGR-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C10H14N4O3/c1-6(15)4-14-5-11-8-7(14)9(16)13(3)10(17)12(8)2/h5-6,15H,4H2,1-3H3
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| Chemical Name |
7-(2-hydroxypropyl)-1,3-dimethylpurine-2,6-dione
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| Synonyms |
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
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| 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) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (10.49 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 (10.49 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 (10.49 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 | 4.1973 mL | 20.9864 mL | 41.9727 mL | |
| 5 mM | 0.8395 mL | 4.1973 mL | 8.3945 mL | |
| 10 mM | 0.4197 mL | 2.0986 mL | 4.1973 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.
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