| Size | Price | |
|---|---|---|
| 100mg | ||
| 250mg | ||
| 500mg |
| ln Vitro |
Heregulin-stimulated HER3 phosphorylation can be prevented by afatinib oxalate at a concentration of 100 nM [1]. Effectively suppressing the anchorage-independent proliferation of NIH-3T3 cells ectopically expressing EGFR mutations as well as the cell proliferation of H1666, H3255, and NCI 1975 cells is achieved with the use of Afatinib oxalate (0-10000 nM) [1]. SLMT-1, EC-1, HKESC-1, and HKESC-2 cells show growth suppression in response to Afatinib oxalate (48–72 hours) [2]. In ESCC cell lines, afatinib oxalate (0–1 μM, 24-48 hours) suppresses the AKT and MAPK pathways as well as EGFR and AKT phosphorylation [2]. HKESC-2 and EC-1 experience G0/G1 cell cycle arrest when exposed to afatinib oxalate (0–1 μM) for 16–48 hours [2]. In HKESC-2 and EC-1, afatinib oxalate (0–1 μM, 24-48 hours) efficiently causes apoptosis [2].
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| ln Vivo |
EGFR, HER2, HER3, and AKT phosphorylation were all significantly downregulated and tumor regression was observed when oral afatinib oxalate (0–20 mg/kg) was administered daily for 25 days [1]. Strongly inhibiting the growth of HKESC-2 tumors was afatinib oxalate (15 mg/kg), taken orally for 5 days, followed by 2 days off, for a duration of 2 weeks [2].
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| Cell Assay |
Cell proliferation assay [1]
Cell Types: NIH-3T3 cells, H1666, H3255 and NCI 1975 Cell Tested Concentrations: 0, 1, 10, 100, 1000, 10000 nM Incubation Duration: Experimental Results: Effective inhibition of NIH- anchorage-dependent proliferation 3T3 Cells ectopically express EGFR mutants. It inhibits the anchorage-independent cell proliferation of multiple lung cancer cell lines (H1666, H3255 and NCI 1975 cells) with IC50 values of 60 nM, 0.7 nM and 99 nM respectively. Cell viability assay[2] Cell Types: HKESC-1, HKESC-2, SLMT-1 and EC-1 Cell Line Tested Concentrations: Incubation Duration: 48 and 72 hrs (hours) Experimental Results: More than 95% growth inhibition was observed. Respective IC50 concentrations at 48 hrs (hours) (HKESC-1=0.078 μM, HKESC-2=0.115 μM, KYSE510=3.182 μM, SLMT-1=4.625 μM and EC-1=1.489 μM) and 72 hrs (hours) (HKESC-1=0.002) μM, HKESC-2=0.002 μM, KYSE510=1.090 μM, SLMT-1=1.161 μM and EC-1=0.109 μM) are all in the lower micromolar range. Western Blot Analysis[2] Cell Types: HKESC-2 cells and EC-1 cells Tested Concentrations: 0, 0.01 a |
| Animal Protocol |
Animal/Disease Models: Athymic NMRI-nu/nu female mice (21–31 g, 5 to 6 weeks old, transgenic mouse lung cancer model and xenograft model) [1]
Doses: 15 mg/kg, 20 mg/kg given Medication: Orally administered daily for 25 days Experimental Results: In a standard xenograft model of the epidermoid cancer cell line A431, tumors Dramatically regressed with a cumulative treatment/control tumor volume ratio (T/C ratio) of 2%, and EGFR and AKT downregulates phosphorylation. Induced regression of large tumors in this HER2-driven model and effectively controlled xenograft tumor formation in the NCIH1975 cell line expressing EGFR L858R/T790M, with a T/C value of 12% at a dose of 20 mg/kg. After 4 weeks of treatment, the tumor was diminished by more than 50%. Downregulates EGFR, HER2 and HER3 phosphorylation. Animal/Disease Models: Sixweeks old female athymic nude mice (nu/nu) (16-20 g)[2] Doses: 15 mg/kg Route of Administration: po (oral gavage), according to a schedule of 5 days plus 2 days of rest , lasted for two weeks. Experimental Results: Str |
| References |
[1]. Li D, et al. BIBW2992, an irreversible EGFR/HER2 inhibitor highly effective in preclinical lung cancer models. Oncogene. 2008 Aug 7;27(34):4702-11.
[2]. Wong CH, et al. Preclinical evaluation of afatinib (BIBW2992) in esophageal squamous cell carcinoma (ESCC). Am J Cancer Res. 2015 Nov 15;5(12):3588-99. [3]. Wang XK, et al. Afatinib circumvents multidrug resistance via dually inhibiting ATP binding cassette subfamily G member 2 in vitro and in vivo. Oncotarget. 2014 Dec 15;5(23):11971-85. [4]. Yoshioka T, et al. Antitumor activity of pan-HER inhibitors in HER2-positive gastric cancer. Cancer Sci. 2018 Apr;109(4):1166-1176. |
| Molecular Formula |
C26H27CLFN5O7
|
|---|---|
| Molecular Weight |
575.97328877449
|
| CAS # |
1398312-64-5
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| Related CAS # |
Afatinib;850140-72-6;Afatinib dimaleate;850140-73-7;(E/Z)-Afatinib;439081-18-2;Afatinib-d6;1313874-96-2
|
| SMILES |
C(=O)(O)C(=O)O.N(C1C=CC(F)=C(Cl)C=1)C1=NC=NC2C=C(O[C@@H]3COCC3)C(NC(=O)/C=C/CN(C)C)=CC1=2
|
| 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 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.) |
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| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.7362 mL | 8.6810 mL | 17.3620 mL | |
| 5 mM | 0.3472 mL | 1.7362 mL | 3.4724 mL | |
| 10 mM | 0.1736 mL | 0.8681 mL | 1.7362 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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