产品说明书

WZ4002

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Chemical Structure| 1213269-23-8 同义名 : -
CAS号 : 1213269-23-8
货号 : A222874
分子式 : C25H27ClN6O3
纯度 : 99%+
分子量 : 494.973
MDL号 : MFCD16621244
存储条件：

粉末 Sealed in dry,Store in freezer, under -20°C

液体 -20°C:3-6个月-80°C:12个月
溶解度 :

DMSO: 9 mg/mL(18.18 mM)，配合低频超声助溶，注意：DMSO长时间开封后，会吸水并导致溶解能力下降，请避免使用长期开封的DMSO
动物实验配方：

30% PEG400+0.5% Tween80+5% propylene glycol+water 30 mg/mL suspension

生物活性
靶点

  • EGFR/ErbB1

    EGFR (L858R/T790M), IC50:8 nM

    EGFR (L858R), IC50:2 nM
描述 A significant portion of patients with lung cancer harbor mutations in the kinase domain of epidermal growth factor receptor (EGFR). WZ4002 is a novel, irreversible EGFR inhibitor with IC50 values of 2 nM, 8 nM, 3 nM, and 2 M for EGFR (L858R), EGFR (L858R/T790M), EGFR (E746_A750), and EGFR (E746_A750/T790M), respectively, in Ba/F3 cells[5]. In NR6 cells stably expressing EGFR L858R/T790M or del E746_A750/T790M, treatment of WZ4002 (0.001 – 10 μM) for 16 hours efficiently inhibited TGF-α-induced phosphorylation of del E746_A750/T790M[6]. When H1975 cells with the EGFR mutations L858R and T790M were incubated with WZ4002 at various concentrations (0.01 – 3 μM) for 72 hours, HFG (20 ng/mL) significantly induced the resistance to WZ4002 whereas E7050 (1 μM) reversed the resistance induced by HFG[7]. By combing WZ4002 (1 μM) and ABT-263 (1 μM), the tumor spheroids of H1975 SR cells were markedly fragmented 24 hours after the treatment and nearly half of the H1975 SR cells underwent apoptotic cell death[8]. WZ4002 (2.5 mg/kg or 25 mg/kg) inhibited EGFR phosphorylation and significantly reduced the tumor volume in both EGFR del E746_A750/T790M and L858R/T790M mice[5].
作用机制 WZ4002 acts as an irreversible, mutant-selective EGFR kinase inhibitor that binds to the active conformation of EGFR with the regulatory C-helix and the DFG segment of the activation loop[5].
细胞研究
细胞系 浓度 检测类型 检测时间 活动说明 数据源
human 16HBE cells Proliferation assay 72 h Antiproliferative activity against human 16HBE cells expressing wild type EGFR after 72 hrs by MTT assay, IC50=0.811 μM 23792318
human 16HBE14o- cells Cytotoxicity assay 72 h Cytotoxicity against human 16HBE14o- cells harboring wild type EGFR assessed as growth inhibition after 72 hrs by MTT assay, IC50=1.355 μM 23668441
human A431 cells Cytotoxicity assay 72 h Cytotoxicity against human A431 cells overexpressing wild type EGFR assessed as growth inhibition after 72 hrs by MTT assay, IC50=1.108 μM 23668441
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

2.02mL

0.40mL

0.20mL

10.10mL

2.02mL

1.01mL

20.20mL

4.04mL

2.02mL
参考文献

[1]Zannetti A, Iommelli F, et al. 3'-deoxy-3'-18F-fluorothymidine PET/CT to guide therapy with epidermal growth factor receptor antagonists and Bcl-xL inhibitors in non-small cell lung cancer. J Nucl Med. 2012 Mar;53(3):443-50.

[2]Zhou W, Ercan D, et al. Novel mutant-selective EGFR kinase inhibitors against EGFR T790M. Nature. 2009 Dec 24;462(7276):1070-4.

[3]Kawabata S, Mercado-Matos JR, et al. Rapamycin prevents the development and progression of mutant epidermal growth factor receptor lung tumors with the acquired resistance mutation T790M. Cell Rep. 2014 Jun 26;7(6):1824-32.

[4]Ercan D, Xu C, et al. Reactivation of ERK signaling causes resistance to EGFR kinase inhibitors. Cancer Discov. 2012 Oct;2(10):934-47.

[5]Zhou W, Ercan D, Chen L, Yun CH, Li D, Capelletti M, Cortot AB, Chirieac L, Iacob RE, Padera R, Engen JR, Wong KK, Eck MJ, Gray NS, Jänne PA. Novel mutant-selective EGFR kinase inhibitors against EGFR T790M. Nature. 2009 Dec 24;462(7276):1070-4.

[6]Lee HJ, Schaefer G, Heffron TP, Shao L, Ye X, Sideris S, Malek S, Chan E, Merchant M, La H, Ubhayakar S, Yauch RL, Pirazzoli V, Politi K, Settleman J. Noncovalent wild-type-sparing inhibitors of EGFR T790M. Cancer Discov. 2013 Feb;3(2):168-81.

[7]Wang W, Li Q, Takeuchi S, Yamada T, Koizumi H, Nakamura T, Matsumoto K, Mukaida N, Nishioka Y, Sone S, Nakagawa T, Uenaka T, Yano S. Met kinase inhibitor E7050 reverses three different mechanisms of hepatocyte growth factor-induced tyrosine kinase inhibitor resistance in EGFR mutant lung cancer. Clin Cancer Res. 2012 Mar 15;18(6):1663-71.

[8]Sakuma Y, Yamazaki Y, Nakamura Y, Yoshihara M, Matsukuma S, Nakayama H, Yokose T, Kameda Y, Koizume S, Miyagi Y. WZ4002, a third-generation EGFR inhibitor, can overcome anoikis resistance in EGFR-mutant lung adenocarcinomas more efficiently than Src inhibitors. Lab Invest. 2012 Mar;92(3):371-83.