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AG490

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Chemical Structure| 133550-30-8 同义名 : Tyrphostin AG490;Tyrphostin B42;Zinc02557947
CAS号 : 133550-30-8
货号 : A205043
分子式 : C17H14N2O3
纯度 : 98%
分子量 : 294.305
MDL号 : MFCD00209833
存储条件：

粉末 Keep in dark place,Inert atmosphere,Store in freezer, under -20°C

液体 -20°C:3-6个月-80°C:12个月
溶解度 :

DMSO: 50 mg/mL(169.89 mM)，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：

5% DMSO+40% PEG300+5% Tween80+50% water 6.25 mg/mL

生物活性
靶点

  • EGFR/ErbB1

    EGFR, IC50:0.1 μM
描述 The epidermal growth factor receptor (EGFR) activates several signaling cascades in response to epidermal growth factor stimulation. One of these signaling events involves tyrosine phosphorylation of signal transducer and activator of transcription (STAT), whereas another involves activation of the phosphatidylinositol 3-OH kinase pathway. Two possibilities for STAT activation exist: a janus kinase (JAK)-dependent and a JAK-independent mechanism[3]. AG 490 is nephroprotective by inhibiting oxidative stress-related Janus activated kinase-2 (JAK2) activation with IC50s 7 μM and 0.1 μM for JAK2 and EGFR, respectively[4]. AG490 is used to inhibit phosphorylation of EGFR and signal transducer and activator of STAT-3, and subsequently reduce invasion and adhesion potential of malignant cells[5]. AG-490 belongs to the tyrphostin family of tyrosine kinase inhibitors, which block protein tyrosine kinases by binding to the substrate-binding site. In a vitro study, EPC2 cells were starved for 48h without EGF and then stimulated with 10 ng/ml EGF for designated time periods at 37°C, washed three times with ice-cold PBS, lysed, and centrifuged for 15 min at 4°C, then 50 μM AG-490 were added during culture. It showed that the AG 490 was the most potent, essentially abolishing migration. Importantly, addition of AG-490 had no effect on the viability of the cells[3]. In a vivo study, one vial of compound containing 5 mg of AG490 was injected into 5 mice (1 mg/mouse) via intraperitoneal (i.p) route. Mice (4 weeks of age) were treated three times per week for 5 consecutive weeks and were euthanized one week after the last injection at week 10. Concentration of Tyrphostin AG 490 was 10 μM. The result showed that AG490 treatment of young non-diabetic NOD mice significantly reduced blood glucose levels[6].
作用机制 AG-490 blocks protein tyrosine kinases by binding to the substrate-binding site[3].
细胞研究
细胞系 浓度 检测类型 检测时间 活动说明 数据源
7TD1-DXM 10 μM Growth Inhibition Assay 72 h inhibits cell growth 23871159
7TD1-DXM 50 μM Apoptosis Assay 48 h induces apoptosis 23871159
7TD1-WD-90 10 μM Growth Inhibition Assay 72 h inhibits cell growth 23871159
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

3.40mL

0.68mL

0.34mL

16.99mL

3.40mL

1.70mL

33.98mL

6.80mL

3.40mL
参考文献

[1]Meydan N, Grunberger T, et al. Inhibition of acute lymphoblastic leukaemia by a Jak-2 inhibitor. Nature. 1996 Feb 15;379(6566):645-8.

[2]Gazit A, Osherov N, et al. Tyrphostins. 2. Heterocyclic and alpha-substituted benzylidenemalononitrile tyrphostins as potent inhibitors of EGF receptor and ErbB2/neu tyrosine kinases. J Med Chem. 1991 Jun;34(6):1896-907.

[3]Andl CD, Mizushima T, Oyama K, Bowser M, Nakagawa H, Rustgi AK. EGFR-induced cell migration is mediated predominantly by the JAK-STAT pathway in primary esophageal keratinocytes. Am J Physiol Gastrointest Liver Physiol. 2004 Dec;287(6):G1227-37.

[4]Gazit A, Osherov N, Posner I, Yaish P, Poradosu E, Gilon C, Levitzki A. Tyrphostins. 2. Heterocyclic and alpha-substituted benzylidenemalononitrile tyrphostins as potent inhibitors of EGF receptor and ErbB2/neu tyrosine kinases. J Med Chem. 1991 Jun;34(6):1896-907.

[5]Caceres-Cortes JR. A potent anti-carcinoma and anti-acute myeloblastic leukemia agent, AG490. Anticancer Agents Med Chem. 2008 Oct;8(7):717-22.

[6]Harvey J, Ashford ML. Role of tyrosine phosphorylation in leptin activation of ATP-sensitive K+ channels in the rat insulinoma cell line CRI-G1. J Physiol. 1998 Jul 1;510 ( Pt 1)(Pt 1):47-61.