WZ4002

Catalog No.S1173

For research use only.

WZ4002 is a novel, mutant-selective EGFR inhibitor for EGFR(L858R)/(T790M) with IC50 of 2 nM/8 nM in BaF3 cell line; does not inhibit ERBB2 phosphorylation (T798I).

WZ4002 Chemical Structure

CAS No. 1213269-23-8

Selleck's WZ4002 has been cited by 34 publications

Purity & Quality Control

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Biological Activity

Description WZ4002 is a novel, mutant-selective EGFR inhibitor for EGFR(L858R)/(T790M) with IC50 of 2 nM/8 nM in BaF3 cell line; does not inhibit ERBB2 phosphorylation (T798I).
Targets
EGFR (L858R) [1]
(BaF3 cells)
EGFR (L858R/T790M) [1]
(BaF3 cells)
2 nM 8 nM
In vitro

WZ4002 inhibits other EGFR genotypes E746_A750 and E746_A750/T790M with IC50 of 2 and 6 nM. Besides, WZ4002 suppresses widetype ERBB2 with an IC50 of 32 nM. WZ4002 inhibits EGFR, AKT and ERK1/2 phosphorylation in NSCLC cell lines and WZ4002 prevents of EGFR phosphorylation in NIH-3T3 cells expressing different EGFR T790M mutant alleles. For WZ4002, kinases that exhibited greater than 95% inhibition relative to the DMSO control at 10 μM are selected for measurement of their dissociation constants. WZ4002, which possesses an ortho-methoxy group at the C2-aniline substituent, is more selective for EGFR compared to WZ3146. WZ4002 is 100-fold less effective at inhibiting phosphorylation of WT EGFR compared to the quinazoline inhibitors. Similarly, WZ4002 prevents EGFR kinase activity of recombinant L858R/T790M protein more potently than of WT EGFR, while the opposite is observed with HKI-272 and gefitinib. [1] In addition, the phosphorylated EGFR of Src TKI-resistant H1975 cells, as well as HCC827 cells, is completely suppressed by the third generation EGFR TKI, WZ4002. [2]

Cell Data
Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
Sf9 cells MnXXSpVv[3Srb36gZZN{[Xl? MknMOlAhdWmwcx?= MVnJcohq[mm2aX;uJI9nKEWJRmKgUFg2QFJibYX0ZY51KCi3bnvuc5dvKG:{aXfpckkh\XiycnXzd4VlKGmwIGPmPUBk\WyuczDwdoUucW6ldXLheIVlKG[xcjC2NEBucW6|IHLl[o9z\SC|dXLzeJJifGViYX7kJGFVWCCjZHTpeIlwdiCkeTDoc41w\2WwZX;1d{B1cW2nLYLld49tfmWmIF\SSXQh[XO|YYmsJGlEPTB;MTDuUS=> MWSyOlI4PTB{OB?=
mouse BA/F3 cells NFHYc3JRem:uaX\ldoF1cW:wIHHzd4F6 MYfBcpRqeHKxbHnm[ZJifGm4ZTDhZ5Rqfmm2eTDh[4FqdnO2IH3veZNmKEKDL1[zJINmdGy|IITyZY5{\mWldHXkJJdqfGhiRVfGVkBGPzR4X1G3OVBg\GWuL2S3PVBOKG23dHHueEwhTUN3ME2yJI5O MX2yNVIxQDhyMh?=
human HCC827 cells MmTiVJJwdGmoZYLheIlwdiCjc4PhfS=> NH63N4c4OiCq NUHzWGtCSW62aYDyc4xq\mW{YYTpeoUh[WO2aY\peJkh[WejaX7zeEBpfW2jbjDIR2M5OjdiY3XscJMhcGG{Yn;ybY5oKEWJRmKg[IVtKEV5NE[tRVc2OCCvdYThcpQh[W[2ZYKgO|IhcHK|IHL5JG1VWyCjc4PhfUwhUUN3ME23JI5O NWrvT|RtOjJ|M{mzOFI>
human PC9 cells NWm0U49sWHKxbHnm[ZJifGmxbjDhd5NigQ>? M2\PRmFvfGmycn;sbYZmemG2aY\lJIFkfGm4aYT5JIFo[Wmwc4Sg[5Jwf3SqLYLld4l{fGGwdDDoeY1idiCSQ{mgZ4VtdHNiZYjwdoV{e2mwZzDFS2ZTKEV5NE\fRVc2OC:WN{mwUUBufXSjboSsJGVEPTB;MUSgcm0> MYGyNVIxQDhyMh?=
NCI-H1975 cells NWW2clFSTnWwY4Tpc44h[XO|YYm= NE\4eIEzKGh? Mn7zTY5pcWKrdHnvckBw\iCHR1\SJGw5PTiUL2S5O|BOKGSxdXLs[UBufXSjboSgdIhwe3Cqb4L5cIF1cW:wIHnuJIh2dWGwIF7DTU1JOTl5NTDj[YxteyCjZoTldkAzKGi{czDifUBndHWxcnXzZ4Vv[2ViYYPzZZktKEmFNUC9NE4xOjNizszN M2jldFI{QTNyOUm0
human 16HBE cells NIP6W2FRem:uaX\ldoF1cW:wIHHzd4F6 NIDS[pU4OiCq MnzLRY51cXC{b3zp[oVz[XSrdnWgZYN1cX[rdImgZYdicW6|dDDoeY1idiBzNljCSUBk\WyuczDlfJBz\XO|aX7nJJdqdGRidInw[UBGT0[UIHHmeIVzKDd{IHjyd{BjgSCPVGSgZZN{[XluIFnDOVA:OC56MUGg{txO NInQeFkzOzd7MkOxPC=>
human A431 cells MVPDfZRwfG:6aXPpeJkh[XO|YYm= MYG3NkBp M2XJXGN6fG:2b4jpZ4l1gSCjZ3HpcpN1KGi3bXHuJGE1OzFiY3XscJMhd3[ncnX4dJJme3Orbnege4lt\CC2eYDlJGVITlJiYYPz[ZN{\WRiYYOg[5Jwf3SqIHnubIljcXSrb36gZYZ1\XJiN{KgbJJ{KGK7IF3UWEBie3OjeTygTWM2OD1zLkGwPEDPxE1? MXyyN|Y3QDR2MR?=
human LoVo cells NXH3[2pPTnWwY4Tpc44h[XO|YYm= NGrufJozKGh? MXvJcohq[mm2aX;uJI9nKHerbHSgeJlx\SCHR1\SJJBpd3OyaH;yfYxifGmxbjDpckBpfW2jbjDMc3ZwKGOnbHzzJIFnfGW{IEKgbJJ{KGK7IH\seY9z\XOlZX7j[UBie3OjeTygTWM2OD1zLkG4JO69VQ>? NXfhNllMOjN7M{C5PVQ>
human 16HBE14o- cells  MlTvR5l1d3SxeHnjbZR6KGG|c3H5 NHO0ZXc4OiCq M1LucGN6fG:2b4jpZ4l1gSCjZ3HpcpN1KGi3bXHuJFE3UEKHMUTvMUBk\WyuczDoZZJjd3Krbnege4lt\CC2eYDlJGVITlJiYYPz[ZN{\WRiYYOg[5Jwf3SqIHnubIljcXSrb36gZYZ1\XJiN{KgbJJ{KGK7IF3UWEBie3OjeTygTWM2OD1zLkO1OUDPxE1? MkTWNlM3Pjh2NEG=
human BEAS2B cells NXfsXZFFS3m2b4TvfIlkcXS7IHHzd4F6 M13GV|czKGh? NYH5N2xuS3m2b4TvfIlkcXS7IHHnZYlve3RiaIXtZY4hSkWDU{LCJINmdGy|IHjhdoJwemmwZzD3bYxlKHS7cHWgSWdHWiCjc4Pld5Nm\CCjczDndo94fGhiaX7obYJqfGmxbjDh[pRmeiB5MjDodpMh[nliTWTUJIF{e2G7LDDJR|UxRTFwOEGxJO69VQ>? MXqyN|Y3QDR2MR?=
human A549 cells MmHlVJJwdGmoZYLheIlwdiCjc4PhfS=> NGLSW|g4OiCq NYPZWoNrSW62aYDyc4xq\mW{YYTpeoUh[WO2aY\peJkh[WejaX7zeEBsNVKDUzDk[ZBmdmSnboSgbJVu[W5iQUW0PUBk\WyuczDveoVz\XiycnXzd4lv\yCZVDDFS2ZTKGGodHXyJFczKGi{czDifUBOXFRiYYPzZZktKEmFNUC9Nk4yODJizszN MmfGNlQ3ODd3OUG=
human HL7702 cells NHHXNIZRem:uaX\ldoF1cW:wIHHzd4F6 NI\sTZU4OiCq MoDRRY51cXC{b3zp[oVz[XSrdnWgZYN1cX[rdImgZYdicW6|dDDoeY1idiCKTEe3NFIh[2WubIOg[ZhxemW|c3nu[{B4cWy2IIT5dIUhTUeIUjDh[pRmeiB5MjDodpMh[nliTWTTJIF{e2G7LDDJR|UxRTJwN{Og{txO M4DQVlIzOzN7M{Sy
In vivo In a 2-week efficacy study, WZ4002 treatment results in significant tumor regressions compared to vehicle alone in both T790M containing murine models. [1] Treatment with low-dose WZ4002, and high-dose WZ4002 leads to mean decreases in tracer uptake of 26%, and 36%, respectively. [3]

Protocol (from reference)

Kinase Assay:[1]
  • EGFR kinase assays:

    In vitro inhibitory enzyme kinetic assays using recombinant EGFR L858R/T790M and WT protein and are performed using the ATP/NADH coupled assay system in a 96-well format. WZ4002 is added to determine its inhibitory effects.

Cell Research:[1]
  • Cell lines: NSCLC, Ba/F3 cells, NIH-3T3 cells, PC9GR4 cells
  • Concentrations: 0-1 μM
  • Incubation Time: 72 hours
  • Method: The NSCLC, Ba/F3 cells, NIH-3T3 cells, PC9GR4 cells are used and verified to contain EGFR delE746_A750/T790M by direct sequencing. Cell proliferation and growth assays are performed using the MTS assay. Site directed mutagenesis is performed using the Quick Change Site-Directed Mutagenesis kit.
Animal Research:[1]
  • Animal Models: EGFR-TL (T790M/L858R) mice
  • Dosages: 25mg/kg
  • Administration: Gavage

Solubility (25°C)

In vitro

DMSO 13 mg/mL
(26.3 mM)
Water Insoluble
Ethanol Insoluble

In vivo

Add solvents to the product individually and in order
(Data is from Selleck tests instead of citations):
30% PEG400+0.5% Tween80+5% propylene glycol
For best results, use promptly after mixing.

30 mg/mL

Chemical Information

Molecular Weight 494.18
Formula

C25H27ClN6O3

CAS No. 1213269-23-8
Storage 3 years -20°C powder
2 years -80°C in solvent
Smiles CN1CCN(CC1)C2=CC(=C(C=C2)NC3=NC=C(C(=N3)OC4=CC=CC(=C4)NC(=O)C=C)Cl)OC

In vivo Formulation Calculator (Clear solution)

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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.

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Tech Support

Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

Handling Instructions

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