N-{3-[(5-chloro-2-{[4-(4-methylpiperazin-1-yl)phenyl]amino}pyrimidin-4-yl)oxy]phenyl}prop-2-enamide

• ChemBase编号: 72554
• 分子式: C24H25ClN6O2
• 平均质量: 464.9473
• 单一同位素质量: 464.17275175
• SMILES: c1(ccc(cc1)Nc1ncc(c(n1)Oc1cc(ccc1)NC(=O)C=C)Cl)N1CCN(CC1)C
• Canonical SMILES: C=CC(=O)Nc1cccc(c1)Oc1nc(ncc1Cl)Nc1ccc(cc1)N1CCN(CC1)C
• InChI: InChI=1S/C24H25ClN6O2/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)
• InChIKey: APHGZZPEOCCYNO-UHFFFAOYSA-N

名称和登记号

名称

• IUPAC标准名: N-{3-[(5-chloro-2-{[4-(4-methylpiperazin-1-yl)phenyl]amino}pyrimidin-4-yl)oxy]phenyl}prop-2-enamide
• IUPAC传统名: N-{3-[(5-chloro-2-{[4-(4-methylpiperazin-1-yl)phenyl]amino}pyrimidin-4-yl)oxy]phenyl}prop-2-enamide
• 别名: WZ3146

登记号

• CAS号: 1214265-56-1
• PubChem SID: 162037479
• PubChem CID: 44607360

理论计算性质

• Acid pKa: 13.987313
• 质子受体: 6
• 质子供体: 2
• LogD (pH = 5.5): 2.3939667
• LogD (pH = 7.4): 4.152449
• Log P: 4.8164034
• 摩尔折射率: 132.503 cm^3
• 极化性: 49.138046 Å^3
• 极化表面积: 82.62 Å^2
• 可自由旋转的化学键: 7
• 里宾斯基五规则: true

分子性质

理化性质

• 溶解度: DMSO

安全信息

• 保存条件: -20°C

药理学性质

• 作用靶点: EGFR

产品相关信息

• 成盐信息: Free Base

详细说明

Selleck Chemicals - S1170

Research Area

• Description: Cancer

Biological Activity

• Description: WZ3146 is a mutant-selective irreversible inhibitor of EGFR(L858R) and EGFR(E746_A750) with IC50 of 2 nM and 2 nM, respectively.
• Targets: EGFR L858R; EGFR E746_A750; EGFR L858R/T790M; EGFR E746_A750/T790M
• IC50: 2 nM; 2 nM; 5 nM; 14 nM ^[1]
• In Vitro: WZ3146 significantly suppresses the growth of EGFR mutation containing cell lines with IC50 of 3 nM in EGFR Del E746_A750 containing HCC827 cells, 15 nM in EGFR Del E746_A750 containing PC9 cells, 29 nM in EGFR L858R/T790M containing H1975 cells and 3 nM in EGFR Del E746_A750/T790M containing PC9 GR cells. ^[1]
• Features: Mutant-selective, irreversible

Protocol

• Protocol: Kinase Assay ^[1]
• In-vitro inhibitory enzyme kinetic assays: The assays are carried out in triplicate using the ATP/NADH coupled assay system in a 96-well format. The final reaction mixture contains 0.5 mg/mL Bovine Serum Albumin (BSA), 2 mM MnCl₂, 1 mM phospho(enol) pyruvic acid (PEP), 1 mM TCEP, 0.1 M Hepes 7.4, 2.5 mM poly-[Glu4Tyr1] peptide, 1/50 of the final reaction mixture volume of pyruvate kinase/lactic dehydrogenase enzymes from rabbit muscle, 0.5 mM NADH, 0.5 μM EGFR kinase, 100 μM ATP and varied amount of WZ3146. WZ3146 and ATP are mixed and made separate stock from the mixture with all other ingredients and added last to the latter to start the reaction. Steady state initial velocity data are drawn from the slopes of the A340 curves.
• Protocol: Cell Assay ^[1]
• Cell Lines: NSCLC and Ba/F3 cells
• Concentrations: 0-10 μM
• Incubation Time: 72 hours
• Methods: Growth and inhibition of growth is assessed by MTS assay. NSCLC or Ba/F3 cells are exposed to treatment for 72 hours and the number of cells used per experiment is determined empirically. All experimental points are set up in six to twelve wells and all experiments are repeated at least three times. The data is graphically displayed using GraphPad Prism version 5.0 for Windows. The curves are fitted using a non-linear regression model with a sigmoidal dose response.

References

• References: [1] Zhou W, et al. Nature, 2009, 462(7276), 1070-1074.

参考文献

• Zhou W, et al. Nature, 2009, 462(7276), 1070-1074.