Entrectinib (Synonyms: NMS-E628, RXDX-101) |
| Catalog No.GC14476 |
L'entrectinib (NMS-E628) est un puissant inhibiteur pan-Trk, ROS1 et ALK, disponible par voie orale et actif sur le SNC. L'entrectinib inhibe TrkA, TrkB, TrkC, ROS1 et ALK avec des valeurs d'IC50 de 1, 3, 5, 12 et 7 nM, respectivement. Activité antitumorale.
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 1108743-60-7
Sample solution is provided at 25 µL, 10mM.
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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]: | |
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Cell lines |
SH-SY5Y cells stably transfected with TrkB |
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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. |
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Reacting condition |
1 ~ 200 nM; 1 hr |
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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]: | |
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Animal models |
Nu/nu mice bearing SY5Y-TrkB cells |
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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. |
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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. |
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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 | |
| Synonymes | NMS-E628, RXDX-101 | ||
| 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 | ||
| 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 | ||
| Formula | C31H34F2N6O2 | M.Wt | 560.64 |
| Solubility | ≥ 28.05mg/mL in DMSO | Storage | Store at -20°C |
| General tips | Please select the appropriate solvent to prepare the stock solution according to the
solubility of the product in different solvents; once the solution is prepared, please store it in
separate packages to avoid product failure caused by repeated freezing and thawing.Storage method
and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored
at -20°C, please use it within 1 month. To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time. |
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| Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. | ||
| Prepare stock solution | |||
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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 |
Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)
g
μL
Step 2: Enter the in vivo formulation (This is only the calculator, not formulation. Please contact us first if there is no in vivo formulation at the solubility Section.)
Calculation results:
Working concentration: mg/ml;
Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid concentration mg/mL, Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug. )
Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O, mix and clarify.
Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.
Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such as vortex, ultrasound or hot water bath can be used to aid dissolving.
3. All of the above co-solvents are available for purchase on the GlpBio website.
Quality Control & SDS
- View current batch:
- Purity: >99.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Average Rating: 5 (Based on Reviews and 32 reference(s) in Google Scholar.)
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