| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
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| Other Sizes |
| Targets |
The primary targets of Axitinib-13C,d3 are VEGFR1, VEGFR2, VEGFR3, c-kit, and PDGFRβ. Axitinib blocks the activation of these targets, with IC50 values of 1.2, 0.25, 0.29, 1.7, and 1.6 nM, respectively. By inhibiting these receptor tyrosine kinases, it blocks angiogenesis and tumor growth. The labeled compound is used to study these interactions in the context of pharmacokinetics.
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|---|---|
| ln Vitro |
Drug compounds have included stable heavy isotopes of carbon, hydrogen, and other elements, mostly as quantitative tracers while the drugs were being developed. Because deuteration may have an effect on a drug's pharmacokinetics and metabolic properties, it is a cause for concern [1].
In vitro, Axitinib-13C,d3, like Axitinib, inhibits the kinase activity of VEGFR1, VEGFR2, VEGFR3, c-kit, and PDGFRβ. It has been shown to inhibit VEGF-mediated endothelial cell proliferation and survival. The compound's inhibitory activity is typically assessed using kinase assays and cell-based proliferation assays. These in vitro studies confirm its potent anti-angiogenic and anti-tumor activity. |
| ln Vivo |
In vivo, Axitinib-13C,d3 is used as a tracer to study the pharmacokinetics and metabolism of Axitinib in animal models. Axitinib has demonstrated significant anti-tumor activity in xenograft models of renal cell carcinoma and other solid tumors. The deuterated and 13C-labeled form is used to accurately quantify the parent drug and its metabolites in biological samples using mass spectrometry.
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| Enzyme Assay |
Cell-free assays for Axitinib-13C,d3 typically involve measuring its inhibitory activity against VEGFR1, VEGFR2, VEGFR3, c-kit, and PDGFRβ using biochemical kinase assays. The IC50 values are determined by measuring the phosphorylation of a substrate in the presence of varying concentrations of the compound. These assays are used to characterize the compound's potency and selectivity.
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| Cell Assay |
In vitro cellular assays are conducted to evaluate the functional activity of Axitinib-13C,d3. Endothelial cells are treated with VEGF in the presence or absence of the compound. VEGFR phosphorylation is measured to assess the inhibition of VEGF-induced signaling. Cell proliferation and migration assays are used to evaluate the compound's anti-angiogenic activity. These assays confirm that Axitinib-13C,d3 effectively blocks VEGF-mediated cellular responses.
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| Animal Protocol |
In vivo animal experiments typically involve xenograft models of cancer. Animals are administered the compound via oral gavage. Tumor growth is monitored over time to assess efficacy. Pharmacokinetic studies are conducted to measure the concentrations of Axitinib and its labeled form in plasma and tissues using LC-MS. The labeled compound is used as an internal standard for accurate quantification.
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| ADME/Pharmacokinetics |
The pharmacokinetic properties of Axitinib-13C,d3 are identical to those of Axitinib. It is orally bioavailable and has a half-life of approximately 4-8 hours in humans. It is metabolized primarily by CYP3A4/5 and undergoes extensive hepatic metabolism. The labeled form is used as an internal standard to accurately measure the pharmacokinetics of Axitinib in biological samples.
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| Toxicity/Toxicokinetics |
The toxicity profile of Axitinib-13C,d3 is similar to that of Axitinib. Common adverse effects associated with Axitinib include hypertension, fatigue, diarrhea, and hand-foot skin reaction. These side effects are related to its mechanism of action as a VEGFR inhibitor. The labeled compound is not intended for therapeutic use and is used only in research settings.
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| References | |
| Additional Infomation |
Axitinib (AG-013736) is a multi-targeted tyrosine kinase inhibitor approved for the treatment of advanced renal cell carcinoma (RCC). Axitinib-13C,d3 is the 13C-labeled and deuterated form used as an analytical standard for research purposes. It is valuable for pharmacokinetic studies and bioanalysis, allowing for the accurate quantification of Axitinib in biological samples using LC-MS.
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| Molecular Formula |
C2113CH15D3N4OS
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|---|---|
| Molecular Weight |
390.48
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| Exact Mass |
390.142
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| CAS # |
1261432-00-1
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| Related CAS # |
Axitinib;319460-85-0
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| PubChem CID |
49849411
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| Appearance |
White to off-white solid powder
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| Density |
1.4±0.1 g/cm3
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| Index of Refraction |
1.728
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| LogP |
4.2
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
4
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| Rotatable Bond Count |
5
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| Heavy Atom Count |
28
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| Complexity |
557
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| Defined Atom Stereocenter Count |
0
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| SMILES |
[2H][13C]([2H])([2H])NC(=O)C1=CC=CC=C1SC2=CC3=C(C=C2)C(=NN3)/C=C/C4=CC=CC=N4
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| InChi Key |
RITAVMQDGBJQJZ-QUYHSVBSSA-N
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| InChi Code |
InChI=1S/C22H18N4OS/c1-23-22(27)18-7-2-3-8-21(18)28-16-10-11-17-19(25-26-20(17)14-16)12-9-15-6-4-5-13-24-15/h2-14H,1H3,(H,23,27)(H,25,26)/b12-9+/i1+1D3
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| Chemical Name |
2-[[3-[(E)-2-pyridin-2-ylethenyl]-1H-indazol-6-yl]sulfanyl]-N-(trideuterio(113C)methyl)benzamide
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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 |
| 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) |
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
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|---|---|
| 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 | 2.5610 mL | 12.8048 mL | 25.6095 mL | |
| 5 mM | 0.5122 mL | 2.5610 mL | 5.1219 mL | |
| 10 mM | 0.2561 mL | 1.2805 mL | 2.5610 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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