WZ4002 |
| Catalog No.GC15494 |
Mutant-selective EGFR inhibitor(L858R,T790M), irreversible and potent
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 1213269-23-8
Sample solution is provided at 25 µL, 10mM.
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WZ4002 is a novel mutant-selective epidermal growth factor receptor (EGFR) kinase inhibitor that potently and irreversibly suppresses the ATP-dependent auto-phosphorylation of both wild-type EGFR and EGFR mutants, including EGFR delE746_A750/T790M, EGFR L858R/T790M, EGFR T790M, EGFR delE746_A750 and EGFR L858R, with inhibition constant Ki of 13.6 nM, 1.8 nM, 4 nM, 5 nM, 3.9 nM and 8.5 nM respectively. Although WZ4002 is actively against EGFR mutants rather than wild-type EGFR at lower concentrations resulting in less toxicity in normal tissues, wild-type EGFR is susceptible to higher concentrations of WZ4002 as well as prolonged administration of WZ4002, especially in tissues where it accumulates.
References:
[1]Lee HJ, Schaefer G, Heffron TP, Shao L, Ye X, Sideris S, Malek S, Chan E, Merchant M, La H, Ubhayakar S, Yauch RL, Pirazzoli V, Politi K, Settleman J. Noncovalent wild-type-sparing inhibitors of EGFR T790M. Cancer Discov. 2013 Feb;3(2):168-81. doi: 10.1158/2159-8290.CD-12-0357. Epub 2012 Dec 10.
[2]Zhou W, 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. doi: 10.1038/nature08622.
[3]Zannetti A, Iommelli F, Speranza A, Salvatore M, Del Vecchio S. 3'-deoxy-3'-18F-fluorothymidine PET/CT to guide therapy with epidermal growth factor receptor antagonists and Bcl-xL inhibitors in non-small cell lung cancer. J Nucl Med. 2012 Mar;53(3):443-50. doi: 10.2967/jnumed.111.096503. Epub 2012 Feb 13.
| Cell experiment [1]: | |
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Cell lines |
EGFR-mutated NSCLC cell lines PC-9 and NCI-H1975 (H1975) |
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Preparation method |
The solubility of this compound in DMSO is >24.7mg/mL. General tips for obtaining a higher concentration: Please warm the tube at 37℃ for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below -20℃ for several months. |
|
Reacting condition |
1-40 nM (PC-9G cells) and 0-1000 nM (H1975 cells); 72 h |
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Applications |
In PC-9G and H1975 cells, WZ4002 alone reduced the cell viability in a small amount, and combining WZ4002 with SAHA significantly decreased cell viability for both cell lines. Combined treatment of WZ4002 with SAHA significantly enhanced bcl-xL decrement, caspase 3 activation and PARP cleavage. In PC-9G cells, combining WZ4002 with SAHA also enhanced autophagy. |
| Animal experiment [1]: | |
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Animal models |
nude mice xenografted with H1975 cells |
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Dosage form |
25 mg/kg; oral gavage for 5 days per week; 3 weeks |
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Application |
In nude mice xenografted with H1975 cells, WZ4002 resulted in only a marginal decrease in tumor volume, whereas treatment with the combination of WZ4002 and SAHA led to a marked shrinkage of tumor. In H1975 tumors, Combined treatment of WZ4002 with SAHA decreased expression of bcl-2 and bcl-xL and increased PARP cleavage, which then enhanced apoptosis and autophagy. |
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Other notes |
Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal. |
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References: [1]. Lee TG1, Jeong EH, Kim SY, et al. The combination of irreversible EGFR TKIs and SAHA induces apoptosis and autophagy-mediated cell death to overcome acquired resistance in EGFR T790M-mutated lung cancer. Int J Cancer. 2015 Jun 1;136(11):2717-29. |
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| Cas No. | 1213269-23-8 | SDF | |
| Chemical Name | N-[3-[5-chloro-2-[2-methoxy-4-(4-methylpiperazin-1-yl)anilino]pyrimidin-4-yl]oxyphenyl]prop-2-enamide | ||
| Canonical SMILES | CN1CCN(CC1)C2=CC(=C(C=C2)NC3=NC=C(C(=N3)OC4=CC=CC(=C4)NC(=O)C=C)Cl)OC | ||
| Formula | C25H27ClN6O3 | M.Wt | 494.18 |
| Solubility | ≥ 24.7mg/mL in DMSO | 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 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.0236 mL | 10.1178 mL | 20.2355 mL |
| 5 mM | 0.4047 mL | 2.0236 mL | 4.0471 mL |
| 10 mM | 0.2024 mL | 1.0118 mL | 2.0236 mL |
Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)
g
μL
Step 2: Enter the in vivo formulation (This is only the calculator, not formulation. Please contact us first if there is no in vivo formulation at the solubility Section.)
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: >98.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Average Rating: 5 (Based on Reviews and 29 reference(s) in Google Scholar.)
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