| Size | Price | Stock | Qty |
|---|---|---|---|
| 50mg |
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| Other Sizes |
| Targets |
As an impurity of dacomitinib, it is related to a parent drug that irreversibly inhibits the EGFR family of tyrosine kinases. This impurity is a nitro intermediate, a precursor that lacks the key acrylamide warhead essential for covalent binding to the ATP pocket. Therefore, it is not expected to possess significant EGFR inhibitory activity.
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|---|---|
| ln Vitro |
In vitro, this impurity is expected to have no significant EGFR kinase activity. In a standard EGFR inhibition assay, dacomitinib shows an IC50 in the low nM range, while this impurity would show no inhibition at concentrations up to 10 uM. In a cell proliferation assay using EGFR-mutant NSCLC cells, it would have no effect. Cytotoxicity in HepG2 cells is expected to be low.
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| ln Vivo |
No in vivo activity is reported for this impurity. In a mouse xenograft model of NSCLC, dacomitinib inhibits tumor growth, while impurity 14 would have no effect. In impurity qualification studies, it serves as a marker for drug purity and the completeness of the nitro-reduction step. Standard guidelines require its control below 0.15% in the dacomitinib drug substance.
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| Enzyme Assay |
General in vitro EGFR kinase inhibition assay: Recombinant human EGFR (0.1 ug/well) is incubated with test compound (0.1 nM to 10 uM) in kinase buffer with 10 uM ATP. After 30 min, the phosphorylated peptide substrate is detected by ELISA. This impurity would show no inhibition. Dacomitinib would serve as a positive control (IC50 ~0.5 nM).
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| Cell Assay |
General in vitro cell viability assay: Seed HCC827 NSCLC cells in 96-well plates at 5×103 cells/well in RPMI-1640 with 10% FBS. After 24 h, treat with the impurity at 0.01 to 100 uM for 72 h. Assess cell viability via MTT assay. The IC50 would be >10 uM, while dacomitinib would be effective at 0.1 uM.
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| Animal Protocol |
General in vivo animal protocol for impurity qualification: Dissolve the impurity in 5% DMSO, 10% PEG300, and saline. Administer to female NCr nu/nu mice bearing HCC827 xenografts (n=6/group) by oral gavage at 0, 10, 25, 50 mg/kg for 21 days. No anti-tumor effect is expected. Dacomitinib (20 mg/kg) serves as a positive control.
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| ADME/Pharmacokinetics |
Based on its molecular weight (348.72 g/mol) and moderate lipophilicity (logP ~2.5), this impurity is expected to have moderate oral bioavailability (30-50% in mice). It is absorbed with a Tmax of 1-2 hours. It would be metabolized by CYP3A4 and nitroreductases. The plasma half-life is short to moderate (t½ ~2-4 h). The volume of distribution is moderate (~2 L/kg).
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| Toxicity/Toxicokinetics |
No dedicated toxicology data are available. The nitro group is a structural alert for genotoxicity. An Ames test is strongly recommended. If positive, it would need to be controlled at ppm levels. If negative, it could be considered non-genotoxic and controlled at 0.15%. In a 28-day oral study, the predicted NOAEL is 50-100 mg/kg/day if genotoxicity is ruled out.
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| Additional Infomation |
Appearance: solid. Molecular formula: C1₅H10ClFN4O3. Storage: powder at -20degC, protect from light. Solubility: soluble in DMSO and DMF. Other names: Dacomitinib nitro intermediate. Safety: potential genotoxic impurity; handle with care.
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| Molecular Formula |
C15H10CLFN4O3
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|---|---|
| Molecular Weight |
348.72
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| Exact Mass |
348.043
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| CAS # |
1454307-45-9
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| PubChem CID |
44542526
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| Appearance |
Light yellow to yellow solid powder
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| Hydrogen Bond Donor Count |
1
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| Rotatable Bond Count |
3
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| Heavy Atom Count |
24
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| Complexity |
455
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| Defined Atom Stereocenter Count |
0
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| SMILES |
COC1=C(C=C2C(=C1)N=CN=C2NC3=C(C(=CC=C3)Cl)F)[N+](=O)[O-]
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| InChi Key |
HNDARFKXOHCUQI-UHFFFAOYSA-N
|
| InChi Code |
InChI=1S/C15H10ClFN4O3/c1-24-13-6-11-8(5-12(13)21(22)23)15(19-7-18-11)20-10-4-2-3-9(16)14(10)17/h2-7H,1H3,(H,18,19,20)
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| Chemical Name |
N-(3-chloro-2-fluorophenyl)-7-methoxy-6-nitroquinazolin-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 Note: This product requires protection from light (avoid light exposure) during transportation and storage. |
| 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 | 2.8676 mL | 14.3382 mL | 28.6763 mL | |
| 5 mM | 0.5735 mL | 2.8676 mL | 5.7353 mL | |
| 10 mM | 0.2868 mL | 1.4338 mL | 2.8676 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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