| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 25mg |
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| 50mg |
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| Other Sizes |
| Targets |
EGFR (epidermal growth factor receptor) and ErbB2 (HER2/neu) tyrosine kinases. As a dual inhibitor, it blocks the kinase activity of both receptors, thereby inhibiting downstream signaling pathways involved in cell proliferation and survival.
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| ln Vitro |
The IC50 value of mitoxantrone against the cell lines ABCG2-482-R2 and ABCG2-482-T7 is decreased by GW 583340 dihydrochloride (5 μM) [1]. The dihydrochloride GW 583340 (2.5 and 7.5 μM, 24 hours) has an IC50 value of when ROS is added to SUM149 and SUM190 cells [1]. In SCCF1 and CatMC cells, GW 583340 dihydrochloride (0–10 μM) decreases colony formation [2].
GW 583340 dihydrochloride has IC50 values of 0.01 µM for EGFR and 0.014 µM for ErbB2. It inhibits the growth of HN5, N87, and BT474 tumor cell lines (which overexpress EGFR and ErbB2) with an IC50 of 0.11 µM. It reverses ABCG2- and ABCB1-mediated drug resistance. |
| ln Vivo |
In mouse xenograft models, GW 583340 dihydrochloride inhibits 80% of tumor growth. This demonstrates significant in vivo antitumor efficacy. It is orally available, suggesting good bioavailability.
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| Enzyme Assay |
The in vitro kinase inhibition assay for GW 583340 dihydrochloride involves measuring the activity of EGFR and ErbB2 kinases in the presence of varying concentrations of the compound. The enzyme is incubated with ATP and a substrate peptide, and the phosphorylation of the substrate is quantified. The IC50 value is determined from the dose-response curve.
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| Cell Assay |
Specific in vitro cell-based assay protocols for GW 583340 dihydrochloride are not detailed. Its effects on cell growth can be assessed in tumor cell lines that overexpress EGFR and/or ErbB2. Cells are treated with GW 583340 dihydrochloride, and cell viability is measured using a standard assay such as MTT or CellTiter-Glo. Its ability to reverse drug resistance can be assessed in cells overexpressing ABCG2 or ABCB1.
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| Animal Protocol |
In mouse xenograft models, GW 583340 dihydrochloride is administered orally to tumor-bearing mice. Tumor growth is monitored, and the inhibition of tumor growth is calculated. This is a standard protocol for evaluating the in vivo efficacy of anticancer compounds.
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| ADME/Pharmacokinetics |
GW 583340 dihydrochloride is orally available, indicating good absorption. Specific pharmacokinetic parameters such as half-life, clearance, and volume of distribution are not provided in the available literature.
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| Toxicity/Toxicokinetics |
Specific toxicological data for GW 583340 dihydrochloride are not available. As a research compound, its safety profile has not been comprehensively characterized. Toxicity studies would be required to determine its safety margin and potential off-target effects.
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| References |
[1]. Sodani K, et al. GW583340 and GW2974, human EGFR and HER-2 inhibitors, reverse ABCG2- and ABCB1-mediated drug resistance. Biochem Pharmacol. 2012 Jun 15;83(12):1613-22.
[2]. Aird KM, et al. ErbB1/2 tyrosine kinase inhibitor mediates oxidative stress-induced apoptosis in inflammatory breast cancer cells. Breast Cancer Res Treat. 2012 Feb;132(1):109-19. [3]. Gray ME,et al. Dual targeting of EGFR and ERBB2 pathways produces a synergistic effect on cancer cell proliferation and migration in vitro. Vet Comp Oncol. 2017 Sep;15(3):890-909. |
| Additional Infomation |
GW 583340 dihydrochloride is a research tool for studying EGFR/ErbB2 signaling and for investigating drug resistance mechanisms. Its dual inhibition and ability to reverse drug resistance make it a valuable compound for cancer research. It is not an approved therapeutic agent.
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| Molecular Formula |
C28H27CL3FN5O3S2
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|---|---|
| Molecular Weight |
671.02
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| Exact Mass |
669.06
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| CAS # |
1173023-85-2
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| PubChem CID |
16219404
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| Appearance |
Typically exists as solid at room temperature
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| Hydrogen Bond Donor Count |
4
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| Hydrogen Bond Acceptor Count |
10
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| Rotatable Bond Count |
11
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| Heavy Atom Count |
42
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| Complexity |
902
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| Defined Atom Stereocenter Count |
0
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| SMILES |
ClC1=C(C=CC(=C1)NC1=C2C(C=CC(=C2)C2=CSC(CNCCS(C)(=O)=O)=N2)=NC=N1)OCC1C=CC=C(C=1)F.Cl.Cl
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| InChi Key |
WIMITXDBYLKRKB-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C28H25ClFN5O3S2.2ClH/c1-40(36,37)10-9-31-14-27-35-25(16-39-27)19-5-7-24-22(12-19)28(33-17-32-24)34-21-6-8-26(23(29)13-21)38-15-18-3-2-4-20(30)11-18;;/h2-8,11-13,16-17,31H,9-10,14-15H2,1H3,(H,32,33,34);2*1H
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| Chemical Name |
N-[3-chloro-4-[(3-fluorophenyl)methoxy]phenyl]-6-[2-[(2-methylsulfonylethylamino)methyl]-1,3-thiazol-4-yl]quinazolin-4-amine;dihydrochloride
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| Synonyms |
GW 583340; GW583340; GW 583340 dihydrochloride
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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 | 1.4903 mL | 7.4513 mL | 14.9027 mL | |
| 5 mM | 0.2981 mL | 1.4903 mL | 2.9805 mL | |
| 10 mM | 0.1490 mL | 0.7451 mL | 1.4903 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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