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NVP-TAE 684

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Chemical Structure| 761439-42-3 同义名 : TAE 684
CAS号 : 761439-42-3
货号 : A215396
分子式 : C30H40ClN7O3S
纯度 : 99%+
分子量 : 614.202
MDL号 : MFCD11977634
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: 6 mg/mL(9.77 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：
生物活性
靶点

  • ALK

    ALK, IC50:3 nM
描述 ALK (anaplastic lymphoma kinase) is a tyrosine kinase that is constitutively activated in certain cancers, following gene alterations such as chromosomal translocation, amplification or point mutation. The fusion protein NPM-ALK, which is generated from a hybrid gene consisting of the intracellular domain of the ALK tyrosine kinase receptor juxtaposed with nucleophosmin, has constitutive tyrosine kinase activity and is associated with 50–60% of cases of anaplastic large-cell lymphomas. NVP-TAE 684 is a potent and selective NPM-ALK kinase inhibitor without exhibiting significant cross-reactivity against other kinases tested, including the highly homologous InsR. Consistent with this, NVP-TAE 684 exhibited inhibitory concentrations (IC50) between 2 and 5nM in NPM-ALK-dependent cells, Ba/F3 NPM-ALK, SU-DHL-1 and Karpas-299, but not the parent Ba/F3-WT cells, with a dose-dependent reduction of NPM-ALK auto-phosphorylation. Through the inhibition of NPM-ALK kinase activity, the downstream signaling events, pSTAT3-Y705 and pSTAT5-Y694, were inhibited in a concentration- (>50nM) and time (50nM, >15min)-dependent manner in Ba/F3 NPM-ALK and Karpas-299 cells. Also, NVP-TAE 684 (>50nM) can lead a dose-dependent reduction in phosphorylation of both ERK and Akt in Karpas-299 cells after 4h of treatment. The G1 phase arrest and apoptosis induced by treatment with 50nM NVP-TAE 684 for 48h can be observed in NPM-ALK-expressing Ba/F3 cells and ALCL patient cell lines. Oral administration of NVP-TAE 684 at dose of 3 and 10mg/kg once daily for 4 weeks significantly delayed lymphoma development in Karpas-299 xenograft mice. Daily oral administration of NVP-TAE 684 at dose of 5 or 10mg/kg for 2 weeks initiated 12 days after Karpas-299 inoculation induced disease regression in mice. Reduction of p-ALK and p-STAT3, as well as CD30 expression (present as the ALCLs) can be observed at day 3 after dose[1].
作用机制 NVP-TAE 684 is expected to bind with the ATP-binding site of ALK.[1]
细胞研究
细胞系 浓度 检测类型 检测时间 活动说明 数据源
697 Growth Inhibition Assay IC50=0.43215 μM SANGER
8-MG-BA Growth Inhibition Assay IC50=2.65414 μM SANGER
A101D Growth Inhibition Assay IC50=1.57113 μM SANGER
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

1.63mL

0.33mL

0.16mL

8.14mL

1.63mL

0.81mL

16.28mL

3.26mL

1.63mL
参考文献

[1]Galkin AV, Melnick JS, et al. Identification of NVP-TAE684, a potent, selective, and efficacious inhibitor of NPM-ALK. Proc Natl Acad Sci U S A. 2007;104(1):270-5.

[2]Tanizaki J, Okamoto I, et al. Combined effect of ALK and MEK inhibitors in EML4-ALK-positive non-small-cell lung cancer cells. Br J Cancer. 2012 Feb 14;106(4):763-7.