TAK-960 dihydrochloride |
| カタログ番号GC37725 |
TAK-960 二塩酸塩は経口投与可能なポロ様キナーゼ 1 (PLK1) の選択的阻害剤であり、IC50 は 0.8 nM です。 TAK-960 二塩酸塩は、PLK2 および PLK3 に対しても阻害活性を示し、IC50 はそれぞれ 16.9 および 50.2 nM です。 TAK-960 二塩酸塩は、複数の癌細胞株の増殖を阻害し、複数の腫瘍異種移植片に対して有意な有効性を示します。
Products are for research use only. Not for human use. We do not sell to patients.
Sample solution is provided at 25 µL, 10mM.
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TAK-960 dihydrochloride is an orally available, selective inhibitor of polo-like kinase 1 (PLK1), with an IC50 of 0.8 nM at 10 μM ATP; TAK-960 dihydrochloride also shows inhibitory activities against PLK2 and PLK3, with IC50s of 16.9 and 50.2 nM, respectively. PLK1|0.8 nM (IC50)|PLK2|16.9 nM (IC50)|PLK3|50.2 nM (IC50)|FAK/PTK2|19.6 nM (IC50)|MLCK/MYLK|25.6 nM (IC50)|FES/FPS|58.2 nM (IC50)
TAK-960 inhibits full-length PLK1 protein with IC50 of 0.8 nM, wich is 20-fold lower than the next lowest IC50 value (PLK2: 16.9 nM). TAK-960 (2-1000 nM) causes accumulation of G2-M cells in HT-29 cells. TAK-960 inhibits proliferation of multiple cancer cell lines, with mean EC50 values ranging from 8.4 to 46.9 nM, but not in nondividing normal cells[1]. TAK-960 (8 nM) leads to G2/M cell cycle arrest without significant cytotoxicity in HeLa cells. TAK-960 does not sensitize cancer cells to radiation when an insufficient amount of time is provided to induce mitotic arrest. The overexpression of a PLK1 mutant, PLK1-R136G&T210D, which is confirmed to cancel the TAK-960-mediated increase in the proportion of mitotic cells, abrogates the radiosensitizing effects of TAK-960[2].
TAK-960 (7.5 mg/kg, p.o.) shows a significant increase in median survival compared with vehicle in MV4-11 human leukemia model. TAK-960 (10 mg/kg, p.o.) inhibits tumor growth in the MDR1-expressing K562ADR-bearing leukemia xenograft model[1]. TAK-960 (10 mg/kg) significantly suppresses tumor growth when combined with IR in tumor xenografts[2].
[1]. Hikichi Y, et al. TAK-960, a novel, orally available, selective inhibitor of polo-like kinase 1, shows broad-spectrum preclinical antitumor activity in multiple dosing regimens. Mol Cancer Ther. 2012 Mar;11(3):700-9. [2]. Inoue M, et al. PLK1 blockade enhances therapeutic effects of radiation by inducing cell cycle arrest at the mitotic phase. Sci Rep. 2015 Oct 27;5:15666.
Kinase experiment: | The inhibitory activity of TAK-960 is assessed by the TR-FRET (fluorescence resonance energy transfer) assay, which measures the ATP-dependent phosphorylation of a biotinylated substrate peptide corresponding to residues 2,470 through 2,488 of the mTOR protein (Biotin-AGAGTVPESIHSFIGDGLV). A total of 288 kinases are screened for TAK-960 inhibition (1 μM) using HotSpot technology and IC50 values for the selected kinases are determined. |
Cell experiment: | Cells are seeded into 96-well plates at 3,000 to 30,000 cells per well in appropriate medium plus 10% fetal calf serum. After 24 hours, cells are treated with serial dilutions of TAK-960, and 72 hours later, the number of viable cells is assessed using the CellTiter-Glo Assay. Calculation of EC50 values and statistical analysis are done using GraphPad Prism software. |
Animal experiment: | The suspension of HeLa cells (2×106 in 100?μL PBS) or H1299 cells (3×106 in 100?μL PBS) is subcutaneously inoculated into the right hind legs of 8-week-old nude mice (BALB/c nu/nu mice). The indicated dose of TAK-960 is orally administered to tumor-bearing mice. In the radiation treatment, tumor xenografts are locally irradiated with the indicated dose of 137Cs γ-rays using a Gammacell 40 Exactor. |
References: [1]. Hikichi Y, et al. TAK-960, a novel, orally available, selective inhibitor of polo-like kinase 1, shows broad-spectrum preclinical antitumor activity in multiple dosing regimens. Mol Cancer Ther. 2012 Mar;11(3):700-9. | |
| Cas No. | SDF | ||
| Canonical SMILES | CN1C2=C(N=C(NC3=CC(F)=C(C(NC4CCN(C)CC4)=O)C=C3OC)N=C2)N(C5CCCC5)CC(F)(F)C1=O.Cl.Cl | ||
| Formula | C27H36Cl2F3N7O3 | M.Wt | 634.52 |
| 溶解度 | DMSO: ≥ 98.57 mg/mL (155.35 mM) | 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 | |||
|
1 mg | 5 mg | 10 mg |
| 1 mM | 1.576 mL | 7.88 mL | 15.7599 mL |
| 5 mM | 315.2 μL | 1.576 mL | 3.152 mL |
| 10 mM | 157.6 μL | 788 μL | 1.576 mL |
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Quality Control & SDS
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- Purity: >99.50%
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Average Rating: 5 (Based on Reviews and 3 reference(s) in Google Scholar.)
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