AST 487 (Synonyms: NVP-AST 487) |
| カタログ番号GC10914 |
多剤作用キナーゼ阻害剤
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 630124-46-8
Sample solution is provided at 25 µL, 10mM.
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AST487 is an inhibitor of RET kinase with IC50 value of 0.88μM [1].
AST487 belongs to the N,N’-diphenyl urea class. It inhibit the activity of RET kinase as well as many other kinases( such as KDR, Flt-3 and c-Kit) in vitro. In the cell assay, the inhibition effect of AST487 is displayed both in PC-RET/PTC3 cells and TT cells, which harbor an endogenous activating point mutation of RET (RETC634W). AST487 decreases RET autophosphorylation and activation of PLCγ and ERK with a dose-dependent manner. Additionally, AST487 is also found to inhibit the growth of human thyroid cancer cell lines with RET, but not BRAF mutations. It supports the selectivity of AST487 for RET. In vivo assay shows that AST487 causes significant reductions in the size of NIH3T3-RETC634W xenografts with doses >30 mg/kg/d and oral administration of AST487 at 50 or 30 mg/kg/d decreases mean tumor volume in mice [1].
References:
[1] Nagako Akeno-Stuart, Michelle Croyle, Jeffrey A. Knauf, et al. The RET kinase inhibitor NVP-AST487 blocks growth and calcitonin gene expression through distinct mechanisms in medullary thyroid cancer cells. Cancer Res. 2007, 67:6956-6964.
| Cell experiment [1]: | |
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Cell lines |
Baf3 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 |
10 min; IC50=34±4 nmol/L |
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Applications |
Data derived from a panel of Baf3 murine pro–B cell lymphoma lines rendered growth factor–independent by transduction with various activated tyrosine kinases, suggested cellular specificity for RET-driven proliferation (IC50 for PTC3-RET–driven Baf3 cells, 34±4 nmol/L), with activity against FLT3 as well, and to a lesser extent,Bcr-ABL–dependent proliferation |
| Animal experiment [1]: | |
|
Animal models |
Female athymic nude mice |
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Dosage form |
50 mg/kg; oral taken |
|
Applications |
NVP-AST487 given p.o. evoked a dose-dependent inhibition of growth of NIH3T3-RETC634W xenografts, with doses >30 mg/kg/d causing significant reductions in tumor size. The effects of the compound on RET expression and phosphorylation in tumor extracts was analyzed 6 h following the final treatment. Reductions in tumor RET phosphorylation in NVP-AST487–treated animals were clearly seen, particularly at doses ≥30 mg/kg. Interestingly, there was also a dose-dependent decrease of RET expression, with one of three tumors analyzed in the 30 mg/kg group and three of three tumors in the 50 mg/kg group showing a dramatic reduction in RET protein levels. |
|
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] Yu K, Toral-Barza L, Shi C, et al. Biochemical, cellular, and in vivo activity of novel ATP-competitive and selective inhibitors of the mammalian target of rapamycin[J]. Cancer research, 2009, 69(15): 6232-6240. | |
| Cas No. | 630124-46-8 | SDF | |
| 同義語 | NVP-AST 487 | ||
| Chemical Name | 1-[4-[(4-ethylpiperazin-1-yl)methyl]-3-(trifluoromethyl)phenyl]-3-[4-[6-(methylamino)pyrimidin-4-yl]oxyphenyl]urea | ||
| Canonical SMILES | CCN1CCN(CC1)CC2=C(C=C(C=C2)NC(=O)NC3=CC=C(C=C3)OC4=NC=NC(=C4)NC)C(F)(F)F | ||
| Formula | C26H30F3N7O2 | M.Wt | 529.56 |
| 溶解度 | ≥ 26.5 mg/mL in DMSO, ≥ 51.2 mg/mL in EtOH | 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 | 1.8884 mL | 9.4418 mL | 18.8836 mL |
| 5 mM | 0.3777 mL | 1.8884 mL | 3.7767 mL |
| 10 mM | 0.1888 mL | 0.9442 mL | 1.8884 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
- View current batch:
- Purity: >99.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Average Rating: 5 (Based on Reviews and 30 reference(s) in Google Scholar.)
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