TAE684 (NVP-TAE684) (Synonyms: TAE 684) |
| Catalog No.GC16694 |
선택적 ALK 억제제
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 761439-42-3
Sample solution is provided at 25 µL, 10mM.
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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.
| Cell experiment: [1] | |
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Cell lines |
Ba/F3 and Ba/F3 NPM-ALK cells |
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Preparation method |
The solubility of this compound in DMSO is <10 mM. 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. |
|
Reaction Conditions |
50 nM, 48 hours |
|
Applications |
Cells were treated with various concentrations of TAE684 for 72 h and were assessed for induction of apoptosis and growth arrest by f low cytometry every 24 h. Treatment with TAE684 increased the number of Annexin V-positive Ba/F3 NPM-ALK cells in a dose- and time-dependent manner, without affecting the survival of the parental Ba/F3 cell line. At 48 h after incubation with TAE684, 85–95% of cells stained Annexin V-positive in several independent experiments. In contrast, no increase in the number of Annexin V-positive cells was seen for parental Ba/F3 cells grown in the presence of IL-3. |
| Animal experiment: [1] | |
|
Animal models |
SCIDbeige mice injected with Karpas-299-luc cells |
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Dosage form |
Oral administration; 1, 3, and 10 mg/kg; once daily |
|
Applications |
After 2 weeks of treatment, we observed a 100-fold reduction in bioluminescence signal in the 3- and 10-mg/kg treatment groups. Although the compound was not efficacious at 1 mg/kg, after 4 weeks of treatment with TAE684 at 3 and 10mg/kg, there was a significant delay in lymphoma development and 100- to 1,000-fold reduction in luminescence signal. The TAE684- (10mg/kg) treated group appeared healthy and did not display any signs of compound- or disease-related toxicity. |
|
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] 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. | |
| Cas No. | 761439-42-3 | SDF | |
| Synonyms | TAE 684 | ||
| Chemical Name | 5-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 | ||
| Canonical SMILES | CC(C)S(=O)(=O)C1=CC=CC=C1NC2=NC(=NC=C2Cl)NC3=C(C=C(C=C3)N4CCC(CC4)N5CCN(CC5)C)OC | ||
| Formula | C30H40ClN7O3S | M.Wt | 614.2 |
| Solubility | ≥ 61.4mg/mL in DMSO with gentle warming, ≥ 33.73 mg/mL in EtOH with ultrasonic | 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 | 1.6281 mL | 8.1407 mL | 16.2813 mL |
| 5 mM | 0.3256 mL | 1.6281 mL | 3.2563 mL |
| 10 mM | 0.1628 mL | 0.8141 mL | 1.6281 mL |
Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)
g
μL
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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
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- Purity: >99.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
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