WZ4002

SKU: orb1300949

Description

WZ4002 is a potent and selective small molecule inhibitor targeting the EGFR mutants L858R and T790M, with IC50 values of 2 nM and 8 nM, respectively. It is a valuable research tool for studying resistance mechanisms in non-small cell lung cancer and has demonstrated efficacy in both cellular assays and preclinical in vivo models.

Research Area

Cardiovascular Research, Signal Transduction

Key Properties

• CAS Number: 1213269-23-8
• MW: 494.97
• Purity: 98.12% (May vary between batches)
• Formula: C₂₅H₂₇ClN₆O₃
• SMILES: O(C)C=1C=C(C=CC1NC=2N=C(OC3=CC(NC(C=C)=O)=CC=C3)C(Cl)=CN2)N4CCN(C)CC4
• Target: EGFR
• Solubility: H2O:< 1 mg/mL (insoluble or slightly soluble);DMSO:11 mg/mL (22.22 mM);Ethanol:< 1 mg/mL (insoluble or slightly soluble)

Bioactivity

• Target IC50:
  EGFR (E746_A750):3 nM (cell assay)|EGFR (E746_A750/T790M):2 nM (cell assay)|EGFR (L858R):2 nM|EGFR (L858R/T790M):8 nM
• 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. Treatment with low-dose WZ4002, and high-dose WZ4002 leads to mean decreases in tracer uptake of 26%, and 36%, respectively.
• 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. 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.
• Cell Research:
  The NSCLC, Ba/F3 cells, NIH-3T3 cells, PC9 gR4 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.(Only for Reference)

Storage & Handling

• Storage: Powder: -20°C for 3 years | In solvent: -80°C for 1 year | Shipping with blue ice/Shipping at ambient temperature.
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Alternative Names

WZ 4002, WZ4002, WZ-4002, inhibit, EGFR, Epidermal growth factor receptor, EGFR (L858R), EGFR (L858R/T790M), ErbB-1, Inhibitor, HER1

Compound Identifiers

PubChem CID

44607530