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Purity: ≥98%
WZ3146 (WZ-3146) is a covalent / irreversible and mutant-selective inhibitor of EGFR (L858R and E746_A750) with potential anticancer activity. It exhibits no effects on ERBB2 phosphorylation (T798I), but it inhibits EGFR (L858R and E746_A750) with IC50s of 2 nM and 2 nM, respectively. When applied to EGFR T790M-containing cell lines in vitro, WZ3146 demonstrates strong anti-proliferative activity.
| Targets |
EGFRL858R (IC50 = 2 nM); EGFRL858R/T790M (IC50 = 5 nM); EGFRE746_A750 (IC50 = 2 nM); EGFRE746_A750/T790M (IC50 = 14 nM); EGFR (IC50 = 24 nM)
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| ln Vivo |
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| Enzyme Assay |
The ATP/NADH coupled assay system in 96-well format is used to perform the assays in triplicate. The final reaction mixture includes the following: 0.5 mg/mL bovine serum albumin (BSA), 2 mM MnCl2, 1 mM phospho(enol) pyruvic acid (PEP), 1 mM TCEP, 0.1 M Hepes 7.4, 2.5 mM poly-[Glu4Tyr1] peptide, 1/50 of the final reaction mixture volume of rabbit muscle-derived pyruvate kinase/lactic dehydrogenase enzymes, 0.5 mM NADH, 0.5 μM EGFR kinase, 100 μM ATP, and varying amounts of WZ3146. To initiate the reaction, ATP and WZ3146 are combined, made into a separate stock from the mixture containing all other ingredients, and then added last to the latter. The slopes of the A340 curves provide steady state initial velocity data.
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| Cell Assay |
The MTS assay measures growth and growth inhibition. A fixed number of NSCLC or Ba/F3 cells are used in each experiment, and the cells are subjected to a 72-hour treatment. Three repetitions are required for every experiment, and each experimental point is set up in six to twelve wells. Windows version 5.0 of GraphPad Prism is used to display the data graphically. Non-linear regression model with sigmoidal dose response is used to fit the curves.
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| Animal Protocol |
The MTS assay is used to evaluate growth and growth inhibition. Ba/F3 cells are treated with WZ3146 for a duration of 72 hours. By using the MTS assay, growth and growth inhibition are evaluated.
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| References | ||
| Additional Infomation |
N-[3-[[5-chloro-2-[4-(4-methyl-1-piperazinyl)anilino]-4-pyrimidinyl]oxy]phenyl]-2-propenamide is a member of piperazines.
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| Molecular Formula |
C24H25CLN6O2
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| Molecular Weight |
464.95
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| Exact Mass |
464.172
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| Elemental Analysis |
C, 62.00; H, 5.42; Cl, 7.63; N, 18.08; O, 6.88
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| CAS # |
1214265-56-1
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| Related CAS # |
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| PubChem CID |
44607360
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| Appearance |
White to off-white solid powder
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| Density |
1.3±0.1 g/cm3
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| Index of Refraction |
1.661
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| LogP |
3.6
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
7
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| Rotatable Bond Count |
7
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| Heavy Atom Count |
33
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| Complexity |
638
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| Defined Atom Stereocenter Count |
0
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| SMILES |
ClC1=C([H])N=C(N=C1OC1=C([H])C([H])=C([H])C(=C1[H])N([H])C(C([H])=C([H])[H])=O)N([H])C1C([H])=C([H])C(=C([H])C=1[H])N1C([H])([H])C([H])([H])N(C([H])([H])[H])C([H])([H])C1([H])[H]
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| InChi Key |
APHGZZPEOCCYNO-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C24H25ClN6O2/c1-3-22(32)27-18-5-4-6-20(15-18)33-23-21(25)16-26-24(29-23)28-17-7-9-19(10-8-17)31-13-11-30(2)12-14-31/h3-10,15-16H,1,11-14H2,2H3,(H,27,32)(H,26,28,29)
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| Chemical Name |
N-[3-[5-chloro-2-[4-(4-methylpiperazin-1-yl)anilino]pyrimidin-4-yl]oxyphenyl]prop-2-enamide
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| Synonyms |
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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 |
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| 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) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (5.38 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (5.38 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.5 mg/mL (5.38 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 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 |
*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.
WZ4002, WZ3146 and WZ8040 are novel EGFR inhibitors, suppress the growth of EGFR T790M containing cell lines and inhibit EGFR phosphorylation. Nature. 2009 Dec 24; 462(7276): 1070–1074. |
WZ4002 is less potent than quinazoline EGFR inhibitors against wild type EGFR in vitro and in vivo. Nature. 2009 Dec 24; 462(7276): 1070–1074. |
WZ4002 inhibits EGFR phosphorylation and induces significant tumor regression in murine models of EGFR T790M. Nature. 2009 Dec 24; 462(7276): 1070–1074. |
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