Size | Price | Stock | Qty |
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2mg |
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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 |
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Purity: ≥98%
WZ8040 is a novel, potent, mutant-selective and covalent / irreversible EGFR(T790M) inhibitor that may have anticancer effects; however, it does not prevent ERBB2 (T798I) from becoming phosphorylated.
Targets |
EGFR Del E746_A750 (IC50 = 1 nM); EGFR Del E746_A750 (IC50 = 6 nM); EGFR L858R (IC50 = 66 nM); EGFR L858R/T790M (IC50 = 9 nM); EGFR Del E746_A750/T790M (IC50 = 8 nM); EGFR E746_A750/MET amp (IC50 >3.3 μM); ERBB2 amp (IC50 = 738 nM); ERBB2 amp(IC50 = 915 nM); ERBB2 Ins G776V, C (IC50 = 744 nM); EGFR & ERBB2 WT (IC50 = 1.82 μM nM)
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ln Vitro |
WZ8040 is 30- to 100-fold more potent than quinazoline-based EGFR inhibitors like CL-387785 and HKI-272 against EGFR T790M and up to 100-fold less potent against wild-type EGFR. With IC50 values of 1 nM, 6 nM, 66 nM, 9 nM, and 8 nM, respectively, WZ8040 treatment potently inhibits the growth of HCC827 (EGFR Del E746_A750), PC9 (EGFR Del E746_A750), H3255 (EGFR L858R), H1975 (EGFR L858R/T790M), and PC9 GR (EGFR Del E746_A750/T790M). With IC50 values of >3.3 μM, 738 nM, 915 nM, 744 nM, and 1.82 μM, respectively, WZ8040 weakly inhibits the growth of HCC827 GR (EGFR E746_A750/MET amp), H1819 (ERBB2 amp), Calu-3 (ERBB2 amp), H1781 (ERBB2 Ins G776V, C), and HN11 (EGFR & ERBB2 WT). In A549 (KRAS mutant) or H3122 (EML4-ALK) cells, WZ8040 is not toxic at concentrations up to 10 μM.[1]
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ln Vivo |
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Cell Assay |
WZ8040 is added to cells at escalating concentrations for a duration of 72 hours. MTS survival assay is used to measure growth.
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Animal Protocol |
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References |
Molecular Formula |
C24H25CLN6OS
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Molecular Weight |
481.01
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Exact Mass |
480.15
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Elemental Analysis |
C, 59.93; H, 5.24; Cl, 7.37; N, 17.47; O, 3.33; S, 6.67
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CAS # |
1214265-57-2
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Related CAS # |
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Appearance |
White to off-white solid powder
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SMILES |
CN1CCN(CC1)C2=CC=C(C=C2)NC3=NC=C(C(=N3)SC4=CC=CC(=C4)NC(=O)C=C)Cl
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InChi Key |
KIISCIGBPUVZBF-UHFFFAOYSA-N
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InChi Code |
InChI=1S/C24H25ClN6OS/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]sulfanylphenyl]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: ≥ 1 mg/mL (2.08 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 10.0 mg/mL clear DMSO stock solution to 400 μL of PEG300 and mix evenly; then add 50 μL of Tween-80 to the above solution and mix evenly; then add 450 μL of 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: ≥ 1 mg/mL (2.08 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 10.0 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.  (Please use freshly prepared in vivo formulations for optimal results.) |
Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
1 mM | 2.0790 mL | 10.3948 mL | 20.7896 mL | |
5 mM | 0.4158 mL | 2.0790 mL | 4.1579 mL | |
10 mM | 0.2079 mL | 1.0395 mL | 2.0790 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. td> |
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. td> |
WZ4002 inhibits EGFR phosphorylation and induces significant tumor regression in murine models of EGFR T790M. Nature. 2009 Dec 24; 462(7276): 1070–1074. td> |