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TAE684 (NVP-TAE684)

现货
Catalog No.
A8251
ALK的有效选择性抑制剂
组合的产品项目
规格价格库存 数量
10mM (in 1mL DMSO)
¥ 1,100.00
现货
5mg
¥ 800.00
现货
10mg
¥ 1,200.00
现货
50mg
¥ 3,200.00
Ship with 10-15 days
100mg
¥ 5,720.00
Ship with 10-15 days

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Background

TAE684 (NVP-TAE684) is a selective inhibitor of ALK with IC50 value of 3 nM [1].

Anaplastic lymphoma kinase (ALK) is an enzyme and plays an important role in the development of the brain and exerts its effects on specific neurons in the nervous system. It has been reported that ALK involves in the pathogenesis of various cancers and serves as an important therapeutic target [1, 2].

TAE684 (NVP-TAE684) is a potent ALK inhibitor and has a different selectivity with the reported ALK inhibitor crizotinib. When tested with ALCL cell lines—Karpas-299 and SU-DHL-1 expressing NPM-ALK, TAE684 (NVP-TAE684) inhibited cell proliferation and cell apoptosis in dose-dependent manner [1]. In lung cancer cell lines harboring wild-type, H694R or E1384K mutant ALKs, TAE684 showed effective inhibition on cell proliferation and phospho-Y1604 ALK expression of H694R or E1384K mutant ALK, but also to a degree higher than that of wild-type ALK [2].

In SCIDbeige mice model with luciferized Karpas-299 cells subcutaneous xenograft, in which the invasion could be detected by a strong bioluminescence signal, oral administration of TAE684 (NVP-TAE684) caused significant reduction of lymphoma develop and 100- to 1000-fold reduction in luminecsene signal at the dose of 3 and 10 mg/kg. And, the group received TAE684 (NVP-TAE684) at the dose of 10 mg/kg appeared healthy and showed no signs of compound- or disease-related toxicity [1].

It is also reported that TAE684 is a potent inhibitor of leucine-rich repeat kinase 2 (LRRK2) with IC50 value of 7.8 nM [3].

References:
[1].  Galkin, A.V., 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): p. 270-5.
[2].  Wang, Y.W., et al., Identification of oncogenic point mutations and hyperphosphorylation of anaplastic lymphoma kinase in lung cancer. Neoplasia, 2011. 13(8): p. 704-15.
[3].  Zhang, J., et al., Characterization of TAE684 as a potent LRRK2 kinase inhibitor. Bioorg Med Chem Lett, 2012. 22(5): p. 1864-9.

Chemical Properties

Physical AppearanceA solid
StorageStore at -20°C
M.Wt614.2
Cas No.761439-42-3
FormulaC30H40ClN7O3S
Solubility≥61.4mg/mL in DMSO with gentle warming, ≥33.73 mg/mL in EtOH with ultrasonic, <2.47 mg/mL in H2O
Chemical Name5-chloro-2-N-[2-methoxy-4-[4-(4-methylpiperazin-1-yl)piperidin-1-yl]phenyl]-4-N-(2-propan-2-ylsulfonylphenyl)pyrimidine-2,4-diamine
SDFDownload SDF
Canonical SMILESCC(C)S(=O)(=O)C1=CC=CC=C1NC2=NC(=NC=C2Cl)NC3=C(C=C(C=C3)N4CCC(CC4)N5CCN(CC5)C)OC
运输条件试用装:蓝冰运输。 其他可选规格:常温运输或根据您的要求用蓝冰运输。
一般建议为了使其更好的溶解,请用37℃加热试管并在超声波水浴中震动片刻。不同厂家不同批次产品溶解度各有差异,仅做参考。若实验所需浓度过大至产品溶解极限,请添加助溶剂助溶或自行调整浓度。

试验操作

细胞实验: [1]

细胞系

Ba/F3和Ba/F3 NPM-ALK细胞

制备方法

该化合物在DMSO中的溶解度小于10 mM,若配制更高浓度的溶液,一般步骤如下:请将试管置于37℃加热10分钟和/或将其置于超声波浴中震荡一段时间。原液于-20℃可放置数月。

反应条件

50 nM,48 hours

实验结果

将细胞用各种浓度的TAE684处理72小时,通过流式细胞仪每24小时评估细胞凋亡的诱导和生长停滞。TAE684以剂量和时间依赖性方式增加膜联蛋白V阳性Ba/F3 NPM-ALK细胞的数量,而不影响亲本Ba/F3细胞系的存活。在几个独立实验中,TAE684孵育48小时后,85-95%的细胞染色显示为膜联蛋白V阳性。相反,在IL-3存在下生长的亲本Ba/F3细胞未观察到膜联蛋白V阳性细胞数目的增加。

动物实验: [1]

动物模型

注射Karpas-299-luc 细胞的SCID-beige 小鼠

给药剂量

口服,1、3和10 mg/kg,每天一次

实验结果

TAE684治疗2周后,3和10 mg/kg治疗组中生物发光信号减少100倍。1 mg/kg剂量的TAE684没有效果,但3和10 mg/kg的TAE684治疗4周后,显著延迟淋巴瘤发展,并且发光信号降低100-1,000倍。TAE684(10 mg/kg)治疗组小鼠表现健康,并且没有任何化合物或疾病相关的毒性迹象。

注意事项

请于室内测试所有化合物的溶解度。虽然化合物的实际溶解度可能与其理论值略有不同,但仍处于实验系统误差的允许范围内。

References:

[1] Galkin A V, Melnick J S, Kim S, et al. Identification of NVP-TAE684, a potent, selective, and efficacious inhibitor of NPM-ALK. Proceedings of the National Academy of Sciences, 2007, 104(1): 270-275.

生物活性

Description TAE684是ALK的有效选择性抑制剂,其IC50为3 nM,其对ALK的抑制效果是胰岛素受体的100倍。
靶点 ALK          
IC50 3 nM          

质量控制

化学结构

TAE684 (NVP-TAE684)

相关生物数据

TAE684 (NVP-TAE684)

相关生物数据

TAE684 (NVP-TAE684)