WZ3146 |
| Catalog No.GC13213 |
Mutant EGFR inhibitor, potent and irreversible
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 1214265-56-1
Sample solution is provided at 25 µL, 10mM.
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WZ3146 is a novel, irreversible inhibitor that specifically inhibits phosphorylation of EGFR(L858R0) and EGFR(E746_A750) with IC50 values of 2nM each.
WZ3146 has been reported to inhibit the phosphorylation of EGFR in the Non–Small-Cell Lung Cancer (NSCLC) cell lines [1]. WZ3146 shows to suppress the growth of EGFR T790M containing cell lines. Besides, Analysis of recombinant EGFR T790M kinase incubated with WZ3146 by electrospray mass spectrometry revealed stoichiometric addition of one inhibitor molecule to the protein. Analysis of a pepsin digest of the modified protein by tandem MS identified Cys 797 as the site of modification thus verifying covalent bond formation between WZ3146 and EGFR [2].
References:
[1] Thanyanan Reungwetwattana, Saravut J. Weroha, Julian R. Molina. Oncogenic Pathways, Molecularly Targeted Therapies, and Highlighted Clinical Trials in Non–Small-Cell Lung Cancer (NSCLC). Clinical Lung Cancer, Volume 13, Issue 4, July 2012, Pages 252-266
[2] Zhou W1, Ercan D, Chen L, Yun CH, Li D, Capelletti M, Cortot AB, Chirieac L, Iacob RE, Padera R, Engen JR, Wong KK, Eck MJ, Gray NS, Jänne PA. Novel mutant-selective EGFR kinase inhibitors against EGFR T790M. Nature. 2009 Dec 24;462(7276):1070-4.
Kinase experiment: | In vitro inhibitory enzyme kinetic assays are carried out in triplicate using the ATP/NADH coupled assay system in a 96-well format. The final reaction mixture contains 0.5mg/mL Bovine Serum Albumin (BSA), 2mM MnCl2, 1mM phospho(enol) pyruvic acid, 1mM TCEP, 0.1M Hepes 7.4, 2.5mM poly-[Glu4Tyr1] peptide, 1/50 of the final reaction mixture volume of pyruvate kinase/lactic dehydrogenase enzymes from rabbit muscle, 0.5mM NADH, 0.5μM EGFR kinase, 100μM ATP and varied amount of inhibitors. Inhibitors and ATP are mixed and made separate stock from the mixture with all other ingredients and added last to the latter to start the reaction. Steady state initial velocity data are drawn from the slopes of the A340 curves[1]. |
Animal experiment: | Growth and inhibition of growth is assessed by MTS assay. Ba/F3 cells are exposed to WZ3146 treatment for 72 hours. Growth and inhibition of growth is assessed by MTS assay[1]. |
References: [1]. Zhou W, et al. Novel mutant-selective EGFR kinase inhibitors against EGFR T790M.Nature. 2009 Dec 24;462(7276):1070-4. | |
| Cas No. | 1214265-56-1 | SDF | |
| Chemical Name | N-(3-((5-chloro-2-((4-(4-methylpiperazin-1-yl)phenyl)amino)pyrimidin-4-yl)oxy)phenyl)acrylamide | ||
| Canonical SMILES | C=CC(NC1=CC=CC(OC2=NC(NC3=CC=C(N4CCN(C)CC4)C=C3)=NC=C2Cl)=C1)=O | ||
| Formula | C24H25ClN6O2 | M.Wt | 464.95 |
| Solubility | ≥ 23.25mg/mL in DMSO with gentle warming | Storage | Store at -20°C |
| General tips | Please select the appropriate solvent to prepare the stock solution according to the
solubility of the product in different solvents; once the solution is prepared, please store it in
separate packages to avoid product failure caused by repeated freezing and thawing.Storage method
and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored
at -20°C, please use it within 1 month. To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time. |
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| Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. | ||
| Prepare stock solution | |||
|
1 mg | 5 mg | 10 mg |
| 1 mM | 2.1508 mL | 10.7538 mL | 21.5077 mL |
| 5 mM | 0.4302 mL | 2.1508 mL | 4.3015 mL |
| 10 mM | 0.2151 mL | 1.0754 mL | 2.1508 mL |
Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)
g
μL
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Calculation results:
Working concentration: mg/ml;
Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid 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 master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O, mix and clarify.
Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.
Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such as vortex, ultrasound or hot water bath can be used to aid dissolving.
3. All of the above co-solvents are available for purchase on the GlpBio website.
Quality Control & SDS
- View current batch:
- Purity: >99.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Average Rating: 5 (Based on Reviews and 1 reference(s) in Google Scholar.)
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