Entrectinib
(Synonyms: 恩曲替尼; NMS-E628; RXDX-101) 目录号 : GC14476
A pan-Trk, ROS1, and ALK inhibitor
Cas No.:1108743-60-7
Sample solution is provided at 25 µL, 10mM.
;)
,-1-7$$$37316672.jpg');)
;)
;)
$$$36806353.jpg');)
;33(7)%EF%BC%9A546-561$$$37156877.jpg');)
;)
;)
;)
%201124-1138.$$$35908550.jpg');)
%20766-780.$$$37100057.jpg');)
%20418-432.$$$36893736.jpg');)
%EF%BC%9A-240-255.$$$35108512.jpg');)
533-545$$$36543525.jpg');)
%201-13.$$$36600053.jpg');)
;)
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
| Cell experiment [1]: | |
|
Cell lines |
SH-SY5Y cells stably transfected with TrkB |
|
Preparation method |
The solubility of this compound in DMSO is > 28.1 mg/mL. General tips for obtaining a higher concentration: Please warm the tube at 37 °C for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below - 20 °C for several months. |
|
Reacting condition |
1 ~ 200 nM; 1 hr |
|
Applications |
In SY5Y-TrkB cells, Entrectinib inhibited Trk phosphorylation in a dose-dependent manner. At the dose as low as 1 nM, Entrectinib significantly inhibited Trk phosphorylation, and complete inhibition was achieved at the concentration of 10 nM or higher concentrations. Meanwhile, Entrectinib showed no effect on the Trk-null parental SH-SY5Y cells. |
| Animal experiment [1]: | |
|
Animal models |
Nu/nu mice bearing SY5Y-TrkB cells |
|
Dosage form |
60 mg/kg; p.o.; b.i.d., 7 days/week |
|
Applications |
Entrectinib significantly inhibited tumor growth and prolonged EFS. Analyses of the tumors collected at different time points after treatment (1, 4 and 6 hrs, respectively) indicated inhibition of TrkB phosphorylation in mice treated with Entrectinib. Moreover, phosphorylation of p-PLCγ, p-Akt and p-Erk was also inhibited in Entrectinib-treated mice. In addition, Western blot results also indicated that phosphoprotein expression was significantly suppressed in xenografts upon Entrectinib treatment. |
|
Other notes |
Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal. |
|
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. | |
| Cas No. | 1108743-60-7 | SDF | |
| 别名 | 恩曲替尼; NMS-E628; RXDX-101 | ||
| 化学名 | (Z)-N-(5-(3,5-difluorobenzyl)-1H-indazol-3(2H)-ylidene)-4-(4-methylpiperazin-1-yl)-2-((tetrahydro-2H-pyran-4-yl)amino)benzamide | ||
| Canonical SMILES | CN1CCN(C2=CC(NC3CCOCC3)=C(C(/N=C4C5=C(NN/4)C=CC(CC6=CC(F)=CC(F)=C6)=C5)=O)C=C2)CC1 | ||
| 分子式 | C31H34F2N6O2 | 分子量 | 560.64 |
| 溶解度 | ≥ 28.05mg/mL in DMSO | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
||
| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
 |
1 mg | 5 mg | 10 mg |
| 1 mM | 1.7837 mL | 8.9184 mL | 17.8368 mL |
| 5 mM | 0.3567 mL | 1.7837 mL | 3.5674 mL |
| 10 mM | 0.1784 mL | 0.8918 mL | 1.7837 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Quality Control & SDS
- View current batch:
- Purity: >99.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet