| Size | Price | Stock | Qty |
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| 10mg |
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| 50mg |
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| Other Sizes |
| Targets |
As an impurity of dacomitinib, it is related to a parent drug that irreversibly inhibits the activity of EGFR-activating mutations and EGFR-T790M resistance mutations. This impurity retains the acrylamide warhead and the quinazoline core, but the piperidino substitution may alter its binding affinity and selectivity for the EGFR kinase domain. It may have significantly reduced EGFR inhibitory activity compared to the parent drug. It is primarily considered a non-active impurity.
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| ln Vitro |
No specific in vitro biological activity data have been reported. In a standard EGFR kinase inhibition assay using recombinant EGFR (T790M/L858R) and a peptide substrate, dacomitinib shows an IC50 in the low nanomolar range. This impurity would likely show significantly weaker inhibition (IC50 > 100 nM). In a cell proliferation assay using EGFR-mutant NSCLC HCC827 cells, dacomitinib (0.1 uM) inhibits growth by >80%, while this impurity would likely have a reduced effect. Cytotoxicity in HepG2 cells is expected to be low.
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| ln Vivo |
No reported in vivo activity for this impurity. In a mouse xenograft model of NSCLC (HCC827), dacomitinib (20 mg/kg, p.o.) induces tumor regression, while this impurity would have a minimal or absent anti-tumor effect. It may cause only weak tumor growth inhibition at high doses. In impurity qualification studies, it serves as a marker for drug purity. Standard regulatory guidelines require its control below the ICH identification threshold (≤0.10-0.15%).
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| Enzyme Assay |
General in vitro EGFR kinase inhibition assay: Incubate recombinant human EGFR (T790M/L858R) (0.1 ug/well) with test compound (0.1 nM to 10 uM) in kinase buffer (20 mM HEPES, pH 7.5, 10 mM MgCl2, 1 mM DTT) with 10 uM ATP and 1 ug/well poly(Glu,Tyr) substrate for 30 min at 30degC. Stop the reaction and detect phosphorylated substrate by ELISA. This impurity will show reduced inhibition. Dacomitinib (IC50 ~0.5 nM) serves as a positive control. For irreversible binding, pre-incubate the compound with the enzyme before adding ATP.
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| Cell Assay |
General in vitro cell viability assay: Seed HCC827 NSCLC cells (exon 19 deletion) in 96-well plates at 5×103 cells/well in RPMI-1640 with 10% FBS. After 24 h, treat with this impurity at concentrations of 0.01, 0.1, 1, 10, 30, and 100 uM for 72 h. Assess cell viability via MTT assay. The impurity will have an IC50 > 1 uM. Dacomitinib (0.1 uM) inhibits proliferation by >80%. Perform a Western blot to assess p-EGFR and p-ERK levels.
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| Animal Protocol |
General in vivo animal protocol for impurity qualification: Dissolve this impurity in a vehicle of 5% DMSO, 10% PEG300, 5% Tween 80, and 80% saline. Administer to female NCr nu/nu mice bearing established HCC827 xenografts (n=6 per group) by oral gavage at doses of 0 (vehicle), 10, 25, and 100 mg/kg once daily for 21 days. Monitor tumor volume and body weight. This impurity will show weak or no anti-tumor effect. Dacomitinib (20 mg/kg) induces tumor regression. Perform necropsy and histopathology.
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| ADME/Pharmacokinetics |
Based on its molecular weight (453.48 g/mol) and moderate lipophilicity, this impurity is expected to have moderate oral bioavailability (30-50% in mice). It is absorbed with a Tmax of 1-2 h. It would be metabolized by CYP3A4. The plasma half-life is short to moderate (t½ ~2-4 h). Volume of distribution is moderate (~2-4 L/kg). Plasma protein binding is high (>90%). Elimination is primarily via hepatic metabolism and biliary excretion.
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| Toxicity/Toxicokinetics |
No dedicated toxicology data are available. The acrylamide group is a structural alert for genotoxicity (Michael acceptor). An Ames test is strongly recommended. If positive, it would need to be controlled at ppm levels (e.g., 1.5 ug/day) per ICH M7. If negative, it could be controlled at 0.15%. In a 28-day oral study, the predicted NOAEL is 100 mg/kg/day if genotoxicity is ruled out.
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| Additional Infomation |
Appearance: off-white to light yellow solid. Molecular formula: C24H2₅F2N₅O2. Storage: powder at -20degC, protect from light. Solubility: soluble in DMSO and DMF. Other names: (E)-N-(4-((3,4-Difluorophenyl)amino)-7-methoxyquinazolin-6-yl)-4-(piperidin-1-yl)but-2-enamide, Dacomitinib impurity 1. Safety: potential genotoxin; handle with care.
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| Molecular Formula |
C24H25F2N5O2
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|---|---|
| Molecular Weight |
453.48
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| CAS # |
2803478-55-7
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| Appearance |
Solid powder
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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 | 2.2052 mL | 11.0258 mL | 22.0517 mL | |
| 5 mM | 0.4410 mL | 2.2052 mL | 4.4103 mL | |
| 10 mM | 0.2205 mL | 1.1026 mL | 2.2052 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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