| Size | Price | |
|---|---|---|
| 500mg | ||
| 1g | ||
| Other Sizes |
| Targets |
Human Endogenous Metabolite
The primary biological targets of theophylline sodium acetate are phosphodiesterases (PDEs), adenosine receptors, and histone deacetylases (HDACs). By inhibiting PDE3 and PDE4, it increases intracellular levels of cyclic AMP (cAMP), leading to relaxation of airway smooth muscle. As an adenosine receptor antagonist, it blocks the bronchoconstrictive effects of adenosine. Its anti-inflammatory effects are mediated through the activation of HDACs, which switch off activated inflammatory genes. This multifaceted mechanism of action makes it effective in treating respiratory diseases. The sodium acetate component does not contribute to the pharmacological activity. |
|---|---|
| ln Vitro |
In order to relax human bronchus and pulmonary arteries, theophylline (1,3-Dimethylxanthine) sodium acetate (1–1000 µM) inhibits cAMP hydrolysis by PDE in homogenates of bronchial tissue[1]. By reducing the antiapoptotic protein Bcl-2, theophylline (1,3-Dimethylxanthine) sodium acetate (10 µg /mL; 24 h; eosinophils) promotes apoptosis[2]. In a concentration-dependent way, theophylline (1,3-Dimethylxanthine) sodium acetate (0-500 µM; 2 h; A549 cells) suppresses the activation of NF-κB, the degradation of I-κBα, and the level of IL-6[3]. Histone deacetylase activity is induced by theophylline (1,3-Dimethylxanthine) sodium acetate (0-1000 µM; 30 min; A549 cells) to reduce the expression of inflammatory genes[4].
In vitro, theophylline inhibits phosphodiesterase activity, leading to increased cAMP levels in cells. It antagonizes adenosine receptors, blocking adenosine-induced responses. It activates histone deacetylases, resulting in the suppression of inflammatory gene expression. The specific IC50 values for PDE inhibition vary depending on the isozyme, with preferential inhibition of PDE3 and PDE4. In vitro studies have demonstrated its ability to relax airway smooth muscle preparations and to inhibit the release of inflammatory mediators from immune cells. The sodium acetate salt form is highly water-soluble. |
| ln Vivo |
Theophylline (1,3-Dimethylxanthine) (100 mg/kg; intraperitoneal; daily, for 9 days; male Swiss mice) suppresses TNF-α and NO while increasing IL-6 and IL-10 levels in mice, exhibiting anti-inflammatory effects [1].
In vivo, theophylline sodium acetate is used clinically as a bronchodilator for the treatment of asthma and COPD. It is administered orally or intravenously, and it produces bronchodilation and improves lung function. The compound has a narrow therapeutic index, and its plasma concentrations must be monitored to avoid toxicity. In animal models, it has been shown to reduce airway hyperresponsiveness and inflammation. Its in vivo effects are mediated by both bronchodilation and anti-inflammatory actions. The pharmacokinetics of theophylline are well-characterized, with metabolism primarily by cytochrome P450 enzymes. |
| Enzyme Assay |
The non-cellular enzyme or receptor binding assay for theophylline sodium acetate involves measuring its inhibition of phosphodiesterase (PDE) activity. This is typically performed using a purified PDE enzyme and a fluorescently labeled or radiolabeled cAMP or cGMP substrate. The assay measures the conversion of the cyclic nucleotide to its non-cyclic form. In the presence of the inhibitor, the rate of hydrolysis is reduced. The IC50 value is determined from the dose-response curve. The compound's selectivity for different PDE isozymes can be assessed by using enzymes from different families.
|
| Cell Assay |
Western Blot Analysis[3]
Cell Types: A549 cells Tested Concentrations: 0, 20, 100 and 500 µM Incubation Duration: 2 hrs (hours) Experimental Results: diminished the expression of NF-κB p65 and I-κBα degradation in a concentration-dependent manner. Western Blot Analysis[2] Cell Types: Eosinophils Tested Concentrations: 10 µg /mL Incubation Duration: 24 hrs (hours) Experimental Results: diminished the expression of Bcl-2. The in vitro cellular assay for theophylline sodium acetate involves treating cells with various concentrations of the compound. For its bronchodilatory effects, airway smooth muscle cells are treated, and the effect on cell contraction or relaxation is measured. For its anti-inflammatory effects, immune cells (e.g., macrophages, T cells) are stimulated with LPS or other activators, and the production of inflammatory cytokines (e.g., TNF-α, IL-6) is measured by ELISA. The effect on HDAC activity can be assessed using a colorimetric or fluorescent HDAC activity assay. Cell viability is assessed to rule out cytotoxicity. |
| Animal Protocol |
Animal/Disease Models: Male Swiss mice[1]
Doses: 100 mg/kg Route of Administration: intraperitoneal (ip)injection; daily, for 9 days Experimental Results: Increased IL -6 and IL-10 levels and inhibited TNF-α and NO. The in vivo animal experiment workflow for theophylline sodium acetate typically involves the use of rodent models of asthma or COPD. For example, in an ovalbumin-induced asthma model, mice are sensitized and challenged with ovalbumin, and the compound is administered at various doses. The effect on airway hyperresponsiveness is measured using a plethysmograph. The inflammatory cell infiltration in the lungs is assessed by bronchoalveolar lavage and histology. The compound's bronchodilatory effect can be measured directly using a tracheal ring preparation. These models are used to evaluate the efficacy of theophylline and its derivatives. |
| References |
| Molecular Formula |
C9H10N4NA2O4
|
|---|---|
| Molecular Weight |
284.18
|
| Exact Mass |
284.05
|
| CAS # |
8002-89-9
|
| Related CAS # |
Theophylline;58-55-9;Theophylline-d6;117490-39-8;Theophylline monohydrate;5967-84-0
|
| PubChem CID |
10221451
|
| Appearance |
Typically exists as solid at room temperature
|
| Boiling Point |
454.1°C at 760 mmHg
|
| Flash Point |
228.4°C
|
| Source |
Endogenously produced metabolite
|
| Hydrogen Bond Donor Count |
0
|
| Hydrogen Bond Acceptor Count |
5
|
| Rotatable Bond Count |
0
|
| Heavy Atom Count |
19
|
| Complexity |
394
|
| Defined Atom Stereocenter Count |
0
|
| SMILES |
[Na].[Na].O=C(C)O.O=C1N(C)C(=O)N(C)C2=C1NC=N2
|
| InChi Key |
KXRNMXPUTQVFOA-UHFFFAOYSA-L
|
| InChi Code |
InChI=1S/C7H8N4O2.C2H4O2.2Na/c1-10-5-4(8-3-9-5)6(12)11(2)7(10)13;1-2(3)4;;/h3,12H,1-2H3;1H3,(H,3,4);;/q;;2*+1/p-2
|
| Chemical Name |
disodium;1,3-dimethyl-2-oxopurin-6-olate;acetate
|
| HS Tariff Code |
2934.99.9001
|
| 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)
|
| Solubility (In Vitro) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
|
|---|---|
| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 3.5189 mL | 17.5945 mL | 35.1890 mL | |
| 5 mM | 0.7038 mL | 3.5189 mL | 7.0378 mL | |
| 10 mM | 0.3519 mL | 1.7594 mL | 3.5189 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.
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
