WZ4002

Alias: WZ-4002; WZ 4002; WZ4002
Cat No.:V0552 Purity: ≥98%
WZ4002 (WZ-4002) is a covalent/irreversible and mutant-selective EGFR (e.g. L858R/T790M) inhibitor with potential antitumor activity.
WZ4002 Chemical Structure CAS No.: 1213269-23-8
Product category: EGFR
This product is for research use only, not for human use. We do not sell to patients.
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Purity & Quality Control Documentation

Purity: ≥98%

Product Description

WZ4002 (WZ-4002) is a covalent/irreversible and mutant-selective EGFR (e.g. L858R/T790M) inhibitor with potential antitumor activity. In the BaF3 cell line, it inhibits EGFR(L858R)/(T790M) with IC50s of 2 nM/8 nM.

Biological Activity I Assay Protocols (From Reference)
Targets
EGFRL858R (IC50 = 2 nM); EGFRL858R/T790M (IC50 = 8 nM); EGFRE746_A750 (IC50 = 3 nM); EGFRE746_A750/T790M (IC50 = 2 nM)
ln Vitro

WZ4002 has an IC50 of 2 and 6 nM against the other EGFR genotypes, E746_A750 and E746_A750/T790M. Furthermore, WZ4002 has an IC50 of 32 nM for suppressing widetype ERBB2. WZ4002 prevents EGFR phosphorylation in NIH-3T3 cells expressing various EGFR T790M mutant alleles and inhibits EGFR, AKT, and ERK1/2 phosphorylation in NSCLC cell lines. Dissociation constant measurements for WZ4002 are performed on kinases that showed more than 95% inhibition at 10 μM in comparison to the DMSO control. WZ4002 is more selective for EGFR than WZ3146 because it has an ortho-methoxy group at the C2-aniline substituent. When compared to quinazoline inhibitors, WZ4002 is 100 times less effective at preventing WT EGFR phosphorylation. Likewise, WZ4002 more effectively inhibits the EGFR kinase activity of the recombinant L858R/T790M protein than does WT EGFR, whereas HKI-272 and gefitinib have the opposite effect.[1] Third-generation EGFR TKI WZ4002 also completely suppresses the phosphorylated EGFR of Src TKI-resistant H1975 cells and HCC827 cells.[2]

ln Vivo
WZ4002 treatment causes significant tumor regressions in both T790M-containing murine models in a 2-week efficacy study when compared to vehicle alone.[1] The mean reductions in tracer uptake caused by treatment with low-dose and high-dose WZ4002 are 26% and 36%, respectively.[3]
Enzyme Assay
In vitro inhibitory enzyme kinetic assays are carried out in a 96-well format utilizing the ATP/NADH coupled assay system with recombinant EGFR L858R/T790M and WT protein. To find out how inhibiting it is, WZ4002 is added.
Cell Assay
EGFR delE746_A750/T790M was found to be present in the NSCLC, Ba/F3, NIH-3T3, and PC9GR4 cells through direct sequencing. The MTS assay is used in assays for cell growth and proliferation. The Quick Change Site-Directed Mutagenesis kit is used to carry out site-directed mutagenesis.
Animal Protocol
In order to induce the expression of mutant EGFR, cohorts of EGFR TL/CCSP-rtTA and EGFR TD/CCSP-rtTA are placed on a doxycycline diet at 5 weeks of age. After six to eight weeks on a doxycycline diet, these mice undergo MRI to record and measure the incidence of lung cancer before being assigned to different treatment study cohorts. Every treatment group consists of a minimum of three mice. Following that, mice are given either vehicle (NMP 13 (10% 1-methyl-2-pyrrolidinone: 90% PEG-300) or WZ4002 at a daily gavage dose of 25 mg/kg. These mice receive a second round of MRIs after two weeks of treatment in order to track how well the medication is working. Tumor burden measurements and MRIs are carried out.
References

[1]. Nature . 2009 Dec 24;462(7276):1070-4.

[2]. Lab Invest . 2012 Mar;92(3):371-83.

[3]. J Nucl Med . 2012 Mar;53(3):443-50.

These protocols are for reference only. InvivoChem does not independently validate these methods.
Physicochemical Properties
Molecular Formula
C25H27CLN6O3
Molecular Weight
494.18
Exact Mass
494.18
Elemental Analysis
C, 60.66; H, 5.50; Cl, 7.16; N, 16.98; O, 9.70
CAS #
1213269-23-8
Appearance
White to beige solid powder
SMILES
CN1CCN(CC1)C2=CC(=C(C=C2)NC3=NC=C(C(=N3)OC4=CC=CC(=C4)NC(=O)C=C)Cl)OC
InChi Key
ITTRLTNMFYIYPA-UHFFFAOYSA-N
InChi Code
InChI=1S/C25H27ClN6O3/c1-4-23(33)28-17-6-5-7-19(14-17)35-24-20(26)16-27-25(30-24)29-21-9-8-18(15-22(21)34-3)32-12-10-31(2)11-13-32/h4-9,14-16H,1,10-13H2,2-3H3,(H,28,33)(H,27,29,30)
Chemical Name
N-[3-[5-chloro-2-[2-methoxy-4-(4-methylpiperazin-1-yl)anilino]pyrimidin-4-yl]oxyphenyl]prop-2-enamide
Synonyms
WZ-4002; WZ 4002; WZ4002
HS Tariff Code
2934.99.9001
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)
Solubility Data
Solubility (In Vitro)
DMSO: ~13 mg/mL (~26.3 mM)
Water: <1 mg/mL
Ethanol: <1 mg/mL
Solubility (In Vivo)
30% PEG400+0.5% Tween80+5% propylene glycol: 30 mg/mL
 (Please use freshly prepared in vivo formulations for optimal results.)
Preparing Stock Solutions 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

*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.

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Note: Chemical formula is case sensitive: C12H18N3O4  c12h18n3o4
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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.
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Biological Data
  • WZ4002

  • WZ4002
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