TAK-593
Based on 1 publication(s) in Google Scholar
TAK-593 is a potent VEGFR and PDGFR family inhibitor with IC50s of 3.2, 0.95, 1.1, 4.3 and 13 nM for VEGFR1, VEGFR2, VEGFR3, PDFGRα and PDFGRβ, respectively.
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- Purity: 99.66%
- CAS No.: 1005780-62-0
- 화학식: C23H23N7O3
- 분자량:445.47
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보관:Powder -20°C, 3 years , 4°C, 2 years ; In solvent -80°C, 2 years , -20°C, 1 year
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Biological Activity
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Chemical Information
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용액&용해도
- Protocol
- 순도&문서
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Publications Citing Use of MedChemExpress (MCE) TAK-593
MoreAll VEGFR Isoforms
More
Biological Activity
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VEGFR1 3.2 nM (IC50) |
VEGFR2 0.95 nM (IC50) |
VEGFR3 1.1 nM (IC50) |
PDGFRα 4.3 nM (IC50) |
PDGFRβ 13 nM (IC50) |
PDGFRαV561D 1 nM (IC50) |
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Cell Line
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Type | Value | Description | References |
|---|---|---|---|---|
| HUVEC | IC50 |
0.3 nM
Compound: 23a, TAK-593
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Antiproliferative activity against VEGF-stimulated HUVECs after 5 days by WST-8 assay
Antiproliferative activity against VEGF-stimulated HUVECs after 5 days by WST-8 assay
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[PMID: 23498918] |
TAK-593 inhibits growth of HUVEC with an IC50 of 0.30 nM. It shows potent inhibitory activity against VEGFR (VEGFR1-3: IC50=3.2, 0.95, 1.1 nM) and PDGFR (PDGFRα, β: IC50=4.3, 13 nM) families. Against other kinases, the IC50 values of TAK-593 are above 100 nM, except for Fms (IC50=10 nM) and Ret (IC50=18 nM) kinases[1]. TAK-593 potently inhibits VEGF- and PDGF-stimulated cellular phosphorylation and proliferation of human umbilical vein endothelial cells and human coronary artery smooth muscle cells. TAK-593 also potently inhibits VEGF-induced tube formation of endothelial cells co-cultured with fibroblasts[2].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
| NCT Number | Sponsor | Condition | Start Date |
Phase
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|---|---|---|---|---|
| NCT01329991 | Plexxikon| | 2011-05 | PHASE1 |
Chemical Information
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CAS No. 1005780-62-0
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Appearance Solid
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분자량 445.47
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화학식 C23H23N7O3
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Color White to light yellow
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SMILES
O=C(C1=CC(C)=NN1C)NC2=CC(OC3=NN4C(C=C3)=NC(NC(C5CC5)=O)=C4)=CC=C2C
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선적
Room temperature in continental US; may vary elsewhere.
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보관
Powder -20°C 3 years 4°C 2 years In solvent -80°C 2 years -20°C 1 year
Publications (1)
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Journal Impact Factor
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Most Recent
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Science
2017 Dec 1;358(6367):eaan4368. PMID: 29191878
용액&용해도
DMSO : ≥ 48.5 mg/mL (108.87 mM; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)
* "≥" means soluble, but saturation unknown.
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 2 years; -20°C, 1 year. When stored at -80°C, please use it within 2 years. When stored at -20°C, please use it within 1 year.
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 2 years; -20°C, 1 year. When stored at -80°C, please use it within 2 years. When stored at -20°C, please use it within 1 year.
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
Select the appropriate dissolution method based on your experimental animal and administration route.
- For the following dissolution methods, please ensure to first prepare a clear stock solution using an In Vitro approach and then sequentially add co-solvents:
- To ensure reliable experimental results, the clarified stock solution can be appropriately stored based on storage conditions. As for the working solution for In Vivo experiments, it is recommended to prepare freshly and use it on the same day.
- The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution. If precipitation or phase separation occurs during preparation, heat and/or sonication can be used to aid dissolution.
Add each solvent one by one: 10% DMSO 40% PEG300 5% Tween-80 45% Saline
Solubility: ≥ 2.67 mg/mL (5.99 mM); Clear solution
This protocol yields a clear solution of ≥ 2.67 mg/mL (saturation unknown).
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (26.7 mg/mL) to 400 μL PEG300, and mix evenly; then add 50 μL Tween-80 and mix evenly; then add 450 μL Saline to adjust the volume to 1 mL.
Preparation of Saline: Dissolve 0.9 g sodium chloride in ddH₂O and dilute to 100 mL to obtain a clear Saline solution.
Add each solvent one by one: 10% DMSO 90% (20% SBE-β-CD in Saline)
Solubility: ≥ 2.67 mg/mL (5.99 mM); Clear solution
This protocol yields a clear solution of ≥ 2.67 mg/mL (saturation unknown).
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (26.7 mg/mL) to 900 μL 20% SBE-β-CD in Saline, and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C, storage for one week): 2 g SBE-β-CD powder is dissolved in 10 mL Saline, completely dissolve until clear.
Please enter the basic information of animal experiments:
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Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.
Please enter your animal formula composition:
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%DMSO +
Recommended: Keep the proportion of DMSO in working solution below 2% if your animal is weak.
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%+
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+%Tween-80 + +
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%Saline +
The co-solvents required include: DMSO, . All of co-solvents are available by MedChemExpress (MCE). , Tween 80. All of co-solvents are available by MedChemExpress (MCE).
Working solution concentration: 0.22 mg/mL
Method for preparing stock solution: mg drug dissolved in μL DMSO. Stock solution concentration: mg/mL.
1. Take μL DMSO stock solution;
2. Add μL .
μL , mix evenly;
3. Then add μL Tween 80, mix evenly;
4. Then add μL
Please ensure that the stock solution in the first step is dissolved to a clear state, and add co-solvents in sequence. You can use ultrasonic heating (ultrasonic cleaner, recommended frequency 20-40 kHz), vortexing, etc. to assist dissolution.
Protocol
Enzyme reactions are performed in 50 mM TrisHCl pH 7.5, 5 mM MnCl2, 5 mM MgCl2, 0.01% Tween-20 and 2 mM DTT, containing 10 μM ATP, 0.1 μg/mL biotinylated polyGluTyr (4:1) and 0.1 nM of VEGFR2. Prior to catalytic initiation with ATP, compound (TAK-593) and enzyme are incubated for 5 min at room temperature (preincubation). The reactions are quenched by the addition of 25 μL of 100 mM EDTA, 10 μg/mL AlphaScreen streptavidine donor beads and 10 μg/mL acceptor beads in 62.5 mM HEPES pH 7.4, 250 mM NaCl, and 0.1% BSA. Plates are incubated in the dark overnight and then read by plate reader[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
HUVECs are seeded into a 96-well plate at 3000 cells/well in Human Endothelial-SFM Growth Medium (Invitrogen) containing 3% fetal bovine serum (FBS) and are incubated overnight at 37 C in a 5% CO2 incubator. Various concentrations of the test compounds (TAK-593) are added in the presence of 60 ng/mL VEGF, and the cells are cultured for a further 5 days. Cellular proliferation is determined by the WST-8 formazan assay using Cell Counting Kit-8[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
Rats: The iv administration in rats is conducted under anesthesia with diethyl ether. At 5, 10 (only for iv dosing), 15, 30 min, and 1, 2, 3, 4, 6, 8, 12, 24, 32 (only for monkeys) and 48 h (only for monkeys) after dosing, blood is taken from the tail vein in rats or from the femoral vein in monkeys. Then, the blood is centrifuged to obtain the plasma fraction. The plasma is kept frozen at 20°C until analysis. The concentration of TAK-593 in plasma is determined by the high-performance liquid chromatography with a fluorescence detector. The excitation and emission are 346 and 420 nm, respectively.
Mice: Test compounds are administered at a dose of 10 mg/kg as a cassette dosing to nonfasted mice (BALB/cAJcl; female). After oral administration, blood samples are collected. The blood samples are centrifuged to obtain the plasma fraction. The plasma samples are deproteinized with acetonitrile containing an internal standard. After centrifugation, the supernatant is diluted with a mixture of 0.01 M ammonium formate solution and acetonitrile (9:1, v/v) and centrifuged again. The compound concentrations in the supernatant are measured by LC/MS/MS[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
순도&문서
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Data Sheet (278 KB)
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SDS (393 KB)
- English - EN (393 KB)
- Français - FR (393 KB)
- Deutsch - DE (393 KB)
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Handling Instructions (2659 KB)
References
[1]. Miyamoto N, et al. Discovery of N-[5-({2-[(cyclopropylcarbonyl)amino]imidazo[1,2-b]pyridazin-6-yl}oxy)-2-methylphenyl]-1,3-dimethyl-1H-pyrazole-5-carboxamide (TAK-593), a highly potent VEGFR2 kinase inhibitor. Bioorg Med Chem. 2013 Apr 15;21(8):2333-2345. [Content Brief]
[2]. Awazu Y, et al. Anti-angiogenic and anti-tumor effects of TAK-593, a potent and selective inhibitor of vascular endothelial growth factor and platelet-derived growth factor receptor tyrosine kinase. Cancer Sci. 2013 Apr;104(4):486-94. [Content Brief]
Complete Stock Solution Preparation Table
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 2 years; -20°C, 1 year. When stored at -80°C, please use it within 2 years. When stored at -20°C, please use it within 1 year.
| Optional Solvent | Concentration Solvent Mass | 1 mg | 5 mg | 10 mg | 25 mg |
|---|---|---|---|---|---|
| DMSO | 1 mM | 2.2448 mL | 11.2241 mL | 22.4482 mL | 56.1205 mL |
| 5 mM | 0.4490 mL | 2.2448 mL | 4.4896 mL | 11.2241 mL | |
| 10 mM | 0.2245 mL | 1.1224 mL | 2.2448 mL | 5.6121 mL | |
| 15 mM | 0.1497 mL | 0.7483 mL | 1.4965 mL | 3.7414 mL | |
| 20 mM | 0.1122 mL | 0.5612 mL | 1.1224 mL | 2.8060 mL | |
| 25 mM | 0.0898 mL | 0.4490 mL | 0.8979 mL | 2.2448 mL | |
| 30 mM | 0.0748 mL | 0.3741 mL | 0.7483 mL | 1.8707 mL | |
| 40 mM | 0.0561 mL | 0.2806 mL | 0.5612 mL | 1.4030 mL | |
| 50 mM | 0.0449 mL | 0.2245 mL | 0.4490 mL | 1.1224 mL | |
| 60 mM | 0.0374 mL | 0.1871 mL | 0.3741 mL | 0.9353 mL | |
| 80 mM | 0.0281 mL | 0.1403 mL | 0.2806 mL | 0.7015 mL | |
| 100 mM | 0.0224 mL | 0.1122 mL | 0.2245 mL | 0.5612 mL |
TAK-593 Related Classifications
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