| Size | Price | |
|---|---|---|
| 250mg | ||
| 500mg | ||
| 1g | ||
| 2g | ||
| 5g |
| Targets |
EGFR
|
|---|---|
| ln Vitro |
Gefitinib dihydrochloride (0.01–0.1 μM, 72 h) enhances anchorage-dependent growth and proliferation, raises ERK signaling, and increases the receptor's phosphotyrosine loading [2]. Significant reductions in EGFRvIII phosphotyrosine loading, EGFRvIII-mediated proliferation, and anchorage-independent growth are observed with gefitinib dihydrochloride (1-2 μM, 72 hours) [2]. Through the STAT6-dependent signaling route, gefitinib diHClide (0.62 μM, 24-72 h) suppresses the M2-like polarization of RAW 264.7 cells generated by IL-13 [3]. M2-like macrophage-promoted invasion and migration are inhibited by gefitinib diHClide (0.62 μM, 72 h) [3]. In NSCLC cell lines (H3255 and HCC827 cells), gefitinib diHClide (0–10 μM, 72 hours) causes apoptosis (induction of BIM protein) [4]. In HCC827 and A549 cells, gefitinib diHClide (100 nM, 24 h) promotes cellular absorption of extracellular vesicles (EVs) and inhibits macropinocytosis [6]. The growth of cisplatin-resistant wtEGFR NSCLC cell lines, H358R and A549R, is more inhibited by gefitinib diHClide (1.5–60 μM, 48 hours) [7].
|
| ln Vivo |
Gefitinib dihydrochloride (oral, 75 mg/kg/d, 21 days) suppresses M2-like polarization of macrophages in an LLC mouse metastatic model [3]. Gefitinib dihydrochloride (orally, 75 mg/kg during the first week, once daily for 5 days per week) abolishes phosphorylation of HER2 and HER3 and signaling through MAPK and Akt in lobular hyperplasia and cancer, Increases MAPK activity and cytokine production in splenocytes, lymph nodes [5]. Gefitinib dihydrochloride (150 mg/kg orally, daily) improves the anticancer activity of cisplatin in H358R xenografts [7].
|
| Cell Assay |
Western Blot Analysis[2]
Cell Types: NR6wtEGFR, NR6W and NR6M Tested Concentrations: 1, 10, 100 μM Incubation Duration: 5 hrs (hours) Experimental Results: Inhibition of EGFR tyrosine phosphorylation. Cell migration assay [3] Cell Types: LLCs Cell Tested Concentrations: 0.62 μM Incubation Duration: 72 h Experimental Results: Eliminated M2-like macrophages promoted the invasion and migration of LLCs. |
| Animal Protocol |
Animal/Disease Models: LLC mouse metastasis model [3]
Doses: 75 mg/kg/d for 21 days. Route of Administration: Oral administration Experimental Results: Reduce the number of lung metastasis nodules, down-regulate the expression of M2 marker genes and the percentage of CD206+ and CD68+ macrophages in tumor tissue. Animal/Disease Models: BALB-NeuT transgenic mouse model [5] Doses: 75 mg/kg in the first week, increasing by 15 mg/kg every other week, one time/day, for 5 days a week, followed by 2 days of no treatment, repeated for 8- 9 weeks. Route of Administration: Oral administration Experimental Results: Treated mice diminished tumor multiplicity from 9.6 to 0.58 (83%) and diminished the number and size of lobules and lobular nodules. |
| References |
[1]. Wakeling AE, et al. ZD1839: an orally active inhibitor of epidermal growth factor signaling with potential for cancer therapy. Cancer Res. 2002 Oct 15;62(20):5749-54.
[2]. Pedersen MW, et al. Differential response to gefitinib of cells expressing normal EGFR and the mutant EGFRvIII. Br J Cancer. 2005 Oct 17;93(8):915-23. [3]. Muhammad Tariq, et al. Gefitinib inhibits M2-like polarization of tumor-associated macrophages in Lewis lung cancer by targeting the STAT6 signaling pathway. Acta Pharmacol Sin. 2017 Nov;38(11):1501-1511. [4]. Mark S Cragg, et al. Gefitinib-induced killing of NSCLC cell lines expressing mutant EGFR requires BIM and can be enhanced by BH3 mimetics. PLoS Med. 2007 Oct;4(10):1681-89; discussion 1690. [5]. Marie P Piechocki, et al. Gefitinib prevents cancer progression in mice expressing the activated rat HER2/neu. Int J Cancer. 2008 Apr 15;122(8):1722-9. [6]. Tomoya Takenaka, et al. Effects of gefitinib treatment on cellular uptake of extracellular vesicles in EGFR-mutant non-small cell lung cancer cells. Int J Pharm. 2019 Dec 15;572:118762. [7]. Amin Li, et al. Gefitinib sensitization of cisplatin-resistant wild-type EGFR non-small cell lung cancer cells. J Cancer Res Clin Oncol. 2020 Jul;146(7):1737-1749. |
| Molecular Formula |
C22H24N4O3FCL.2[HCL]
|
|---|---|
| Molecular Weight |
519.82424
|
| Exact Mass |
518.10546
|
| CAS # |
184475-56-7
|
| Related CAS # |
Gefitinib;184475-35-2
|
| PubChem CID |
19077503
|
| Appearance |
Typically exists as solids (or liquids in special cases) at room temperature
|
| Boiling Point |
628.2ºC at 760 mmHg
|
| Vapour Pressure |
4.9E-16mmHg at 25°C
|
| LogP |
5.89
|
| tPSA |
68.74
|
| SMILES |
[H]Cl.[H]Cl.O1CCN(CCCOC2C(OC)=CC3=NC=NC(NC4=CC=C(F)C(Cl)=C4)=C3C=2)CC1
|
| InChi Key |
OHAYARNLYSPHOJ-UHFFFAOYSA-N
|
| InChi Code |
InChI=1S/C22H24ClFN4O3.2ClH/c1-29-20-13-19-16(12-21(20)31-8-2-5-28-6-9-30-10-7-28)22(26-14-25-19)27-15-3-4-18(24)17(23)11-15;;/h3-4,11-14H,2,5-10H2,1H3,(H,25,26,27);2*1H
|
| Chemical Name |
N-(3-chloro-4-fluorophenyl)-7-methoxy-6-(3-morpholin-4-ylpropoxy)quinazolin-4-amine;dihydrochloride
|
| Synonyms |
184475-56-7; Gefitinib (Dihydrochloride); 4-(3-Chloro-4-fluorophenylamino)-7-methoxy-6-[3-(4-morpholinyl)propoxy]quinazoline dihydrochloride; Gefitinib 2hydrochloride salt; gefitinib dihydrochloride; N-(3-chloro-4-fluorophenyl)-7-methoxy-6-(3-morpholin-4-ylpropoxy)quinazolin-4-amine;dihydrochloride; ZD 1839 Dihydrochloride;ZD-1839 Dihydrochloride;ZD1839 Dihydrochloride; SCHEMBL8208642;
|
| HS Tariff Code |
2934.99.9001
|
| 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)
|
| 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
|
|---|---|
| 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 | 1.9237 mL | 9.6187 mL | 19.2374 mL | |
| 5 mM | 0.3847 mL | 1.9237 mL | 3.8475 mL | |
| 10 mM | 0.1924 mL | 0.9619 mL | 1.9237 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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