切换导航

Entrectinib

现货
Catalog No.
B5859
ALK激酶抑制剂
组合的产品项目
规格价格库存 数量
10mM (in 1mL DMSO)
¥ 1,300.00
现货
5mg
¥ 750.00
现货
25mg
¥ 2,650.00
现货
100mg
¥ 5,950.00
现货

电话: 021-55669583

邮箱: sales@apexbio.cn

全球经销商

Background

The receptor tyrosine kinases (RTKs) play a critical role, controlling cell proliferation, survival, and differentiation of normal cells. The anaplastic lymphoma kinase (ALK), a transmembrane RTK, originally identified in the nucleophosmin (NPM)–ALK chimera of anaplastic large cell lymphoma, has emerged as a novel tumorigenic player in several human cancers. Entrectinib is an orally available small-molecule inhibitor of ALK kinase activity.

In vitro: Entrectinib potently and selectively inhibits the in vitro growth of ALK-driven tumors, with confirmed mechanism of action [1].

In vivo: Since Entrectinib is able to pass the blood-brain barrier, the compound was also tested for efficacy in an xenograft model with ALK positive NSCLC tumors. MRI imaging demonstrated that Entrectinib was able to effectively and control the growth of these intracranial tumors dose-dependently, leading to increased survival [1].

Clinical trial: Entrectinib is an orally available small-molecule inhibitor of ALK kinase activity that is being evaluated in phase I/II clinical study to treat solid cancer

Reference:
[1] Elena Ardini, Maria Menichincheri, Patrizia Banfi, Daniele Casero, M. Laura Giorgini, M. Beatrice Saccardo, Nadia Amboldi, Nilla Avanzi, Paolo Orsini, Antonella Isacchi, Enrico Pesenti, Arturo Galvani. The ALK inhibitor NMS-E628 also potently inhibits ROS1 and induces tumor regression in ROS-driven models. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2092. doi:10.1158/1538-7445.AM2013-2092

Chemical Properties

Physical AppearanceA solid
StorageStore at -20°C
M.Wt560.64
Cas No.1108743-60-7
FormulaC31H34F2N6O2
Solubility≥28.05mg/mL in DMSO
Chemical Name(Z)-N-(5-(3,5-difluorobenzyl)-1H-indazol-3(2H)-ylidene)-4-(4-methylpiperazin-1-yl)-2-((tetrahydro-2H-pyran-4-yl)amino)benzamide
SDFDownload SDF
Canonical SMILESCN1CCN(C2=CC(NC3CCOCC3)=C(C(/N=C4C5=C(NN/4)C=CC(CC6=CC(F)=CC(F)=C6)=C5)=O)C=C2)CC1
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

稳定转染TrkB的SH-SY5Y细胞

制备方法

在DMSO中的溶解度大于28.1 mg/mL。若配制更高浓度的溶液,一般步骤如下:请将试管置于37 °C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 °C可放置数月。

反应条件

1 ~ 200 nM;1小时

实验结果

在SY5Y-TrkB细胞中,Entrectinib呈剂量依赖地抑制Trk磷酸化。在低至1nM的剂量下,Entrectinib显著抑制Trk磷酸化。在10 nM或更高的浓度下,Trk磷酸化被完全抑制。同时,Entrectinib对不表达Trk的母系SH-SY5Y细胞无影响。

动物实验 [1]:

动物模型

携带SY5Y-TrkB细胞的裸小鼠

给药剂量

60 mg/kg;口服给药;每天2次,每周7天

实验结果

Entrectinib显著抑制肿瘤生长并延长EFS。在治疗后的不同时间点(分别为1、4和6小时)收集肿瘤。肿瘤组织分析结果表明,Entrectinib抑制了TrkB磷酸化。此外,Entrectinib也抑制了p-PLCγ、p-Akt和p-Erk磷酸化。同时,蛋白印迹结果也表明,Entrectinib显著抑制异种移植物中的磷酸化蛋白表达。

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]. Iyer R, Wehrmann L, Golden RL, Naraparaju K, Croucher JL, MacFarland SP, Guan P, Kolla V, Wei G, Cam N, Li G, Hornby Z, Brodeur GM. Entrectinib is a potent inhibitor of Trk-driven neuroblastomas in a xenograft mouse model. Cancer Lett. 2016 Mar 28;372(2):179-86.

质量控制

化学结构

Entrectinib