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WZ4002
| Product Name | WZ4002 |
| Price: | Inquiry |
| Catalog No.: | CN00471 |
| CAS No.: | 1213269-23-8 |
| Molecular Formula: | C25H27ClN6O3 |
| Molecular Weight: | 494.18 g/mol |
| Purity: | >=98% |
| Type of Compound: | Alkaloids |
| Physical Desc.: | Powder |
| Source: | |
| Solvent: | Chloroform, Dichloromethane, Ethyl Acetate, DMSO, Acetone, etc. |
| SMILES: | C=CC(=O)Nc1cccc(c1)Oc1nc(ncc1Cl)Nc1ccc(cc1OC)N1CCN(CC1)C |
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| Description | WZ4002 is a mutant selective EGFR inhibitor with IC50s of 2, 8, 3 and 2 nM for EGFRL858R, EGFRL858R/T790M, EGFRE746_A750 and EGFRE746_A750/T790M, respectively. |
| Target | EGFRL858R:2 nM (IC50, Cell Assay) EGFRL858R/T790M:8 nM (IC50, Cell Assay) EGFRE746_A750:3 nM (IC50, Cell Assay) EGFRE746_A750/T790M:2 nM (IC50, Cell Assay) |
| In Vitro | WZ4002 increases cellular potency correlated with inhibition of EGFR, AKT and ERK1/2 phosphorylation in NSCLC cell lines and EGFR phosphorylation in NIH-3T3 cells expressing different EGFRT790M mutant alleles. WZ4002 inhibits EGFR kinase activity of recombinant L858R/T790M protein more potently than of WT EGFR[1]. |
| In Vivo | In a pharmacodynamic study WZ4002 effectively inhibits EGFR, AKT and ERK1/2 phosphorylation which is associated with a significant increase in TUNEL positive and a significant decrease in Ki67 positive cells compared to vehicle alone treated mice. In a 2 week efficacy study, WZ4002 treatment results in significant tumor regressions compared to vehicle alone in both T790M containing murine models. Histological evaluation of the lungs following treatment confirms significant resolution of the tumor nodules with only few small residual nodules and nodule remnants that has evidence of treatment effect with decreased cellularity and increased fibrosis consistent with remodeling/scarring[1]. |
| Cell Assay | Growth and inhibition of growth is assessed by MTS assay. Ba/F3 cells are exposed to WZ4002 treatment for 72 hours. Growth and inhibition of growth is assessed by MTS assay[1]. |
| Animal Admin | Cohorts of EGFR TL/CCSP-rtTA and EGFR TD/CCSP-rtTA are put on doxycycline diet at 5 weeks of age to induce the expression of mutant EGFR. These mice undergo MRI after 6 to 8 weeks of doxycycline diet to document and quantify the lung cancer burden before being assigned to various treatment study cohorts. There is a minimum of 3 mice per treatment group. Mice are then treated either with vehicle (NMP 13 (10% 1-methyl-2-pyrrolidinone: 90% PEG-300) alone or WZ4002 at 25mg/kg gavage daily. After 2 weeks of treatment, these mice undergo a second round of MRI to document their response to the treatment. MRIs and tumor burden measurement are performed[1]. |
| Density | 1.3±0.1 g/cm3 |
| Exact Mass | 494.183319 |
| PSA | 95.34000 |
| LogP | 3.48 |