| Size | Price | |
|---|---|---|
| 500mg | ||
| 1g | ||
| Other Sizes |
| Targets |
The primary biological target of Erlotinib-13C6 is the epidermal growth factor receptor (EGFR), a receptor tyrosine kinase that is often overexpressed or mutated in various cancers, including non-small cell lung cancer. Erlotinib binds reversibly to the ATP-binding site of the EGFR tyrosine kinase domain, inhibiting autophosphorylation and downstream signaling pathways that promote cell proliferation, survival, and angiogenesis. The 13C labeling does not alter the binding affinity or selectivity of the molecule for EGFR. The inhibition of EGFR signaling leads to cell cycle arrest and apoptosis in EGFR-dependent tumor cells.
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|---|---|
| ln Vitro |
In intact tumor cells, erlotinib inhibits EGFR autophosphorylation with an IC50 of 20 nM. Non-small cell lung cancer is treated with erlotinib[1]. Throughout the drug development process, stable heavy isotopes of carbon, hydrogen, and other elements have been added to pharmacological compounds, mostly as tracers for quantitation[2].
In vitro, erlotinib, the parent compound of Erlotinib-13C6, inhibits EGFR tyrosine kinase activity with an IC50 of 2 nM for the human EGFR. In intact tumor cells, it effectively reduces EGFR autophosphorylation with an IC50 of 20 nM. These values indicate potent target inhibition at the cellular level. The 13C-labeled analog is expected to exhibit identical in vitro potency and selectivity. It is used as a reference standard to ensure the accuracy of quantification in biological samples. The compound is soluble in DMSO and is typically stored under conditions recommended to maintain stability. |
| ln Vivo |
Information regarding the in vivo activity of Erlotinib-13C6 specifically is not applicable, as it is an analytical standard. However, the parent compound, erlotinib, has demonstrated significant in vivo antitumor activity in animal models and in human clinical trials. In xenograft models, oral administration of erlotinib inhibits tumor growth in an EGFR-dependent manner. In humans, it has shown efficacy in NSCLC, particularly in patients with activating EGFR mutations. The 13C-labeled version is used to quantify erlotinib levels in plasma and tissues from such studies, facilitating pharmacokinetic analysis.
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| Enzyme Assay |
The non-cellular enzyme binding assay for Erlotinib-13C6 is identical in principle to that for erlotinib. It involves measuring the inhibition of EGFR tyrosine kinase activity using a purified recombinant EGFR enzyme and a synthetic peptide substrate. The assay is typically performed using a time-resolved fluorescence resonance energy transfer (TR-FRET) or a radioactive filter-binding method. The phosphorylation of the peptide substrate is measured in the presence of various concentrations of the compound. The IC50 value is calculated from the dose-response curve, reflecting the compound's potency in inhibiting the kinase activity.
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| Cell Assay |
The in vitro cellular assay for Erlotinib-13C6 is performed using cancer cell lines that express EGFR, such as A431 or HCC827 cells. Cells are treated with various concentrations of the compound for a specified period (e.g., 24-72 hours). The effect on EGFR autophosphorylation is assessed by western blotting using phospho-specific EGFR antibodies. Cell viability is measured using MTT or CellTiter-Glo assays to determine the IC50. Apoptosis is evaluated by flow cytometry with Annexin V/PI staining or by measuring caspase-3/7 activity. These assays confirm the functional inhibition of EGFR signaling in a cellular context.
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| Animal Protocol |
The in vivo animal experiment workflow for Erlotinib-13C6 is not for evaluating its efficacy but for use as an analytical standard in pharmacokinetic studies. A typical workflow involves administering unlabeled erlotinib to mice or rats, collecting blood or tissue samples at various time points, and then processing the samples for LC-MS/MS analysis. Erlotinib-13C6 is added to the samples as an internal standard to correct for variations in sample preparation and ionization efficiency. The concentration of erlotinib in the samples is then determined by comparing the signal ratio of erlotinib to the internal standard against a calibration curve.
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| References |
| Molecular Formula |
C22H23N3O4
|
|---|---|
| Molecular Weight |
399.39
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| Exact Mass |
399.188
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| CAS # |
1211107-68-4
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| Related CAS # |
Erlotinib;183321-74-6;Erlotinib-d6;1034651-23-4
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| PubChem CID |
49849307
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| Appearance |
Typically exists as solid at room temperature
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| LogP |
3.3
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| tPSA |
74.7
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
7
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| Rotatable Bond Count |
11
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| Heavy Atom Count |
29
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| Complexity |
525
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| Defined Atom Stereocenter Count |
0
|
| SMILES |
COCCOC1=C(C=C2C(=C1)C(=NC=N2)N[13C]3=[13CH][13CH]=[13CH][13C](=[13CH]3)C#C)OCCOC
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| InChi Key |
AAKJLRGGTJKAMG-GQGGUIAASA-N
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| InChi Code |
InChI=1S/C22H23N3O4/c1-4-16-6-5-7-17(12-16)25-22-18-13-20(28-10-8-26-2)21(29-11-9-27-3)14-19(18)23-15-24-22/h1,5-7,12-15H,8-11H2,2-3H3,(H,23,24,25)/i5+1,6+1,7+1,12+1,16+1,17+1
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| Chemical Name |
N-(5-ethynyl(1,2,3,4,5,6-13C6)cyclohexa-1,3,5-trien-1-yl)-6,7-bis(2-methoxyethoxy)quinazolin-4-amine
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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 | 2.5038 mL | 12.5191 mL | 25.0382 mL | |
| 5 mM | 0.5008 mL | 2.5038 mL | 5.0076 mL | |
| 10 mM | 0.2504 mL | 1.2519 mL | 2.5038 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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