| CAS NO: | 1137868-52-0 |
| 规格: | ≥98% |
| 包装 | 价格(元) |
| 5mg | 电议 |
| 10mg | 电议 |
| 25mg | 电议 |
| 50mg | 电议 |
| 100mg | 电议 |
| 250mg | 电议 |
| 500mg | 电议 |
| Name: TAK-960 dihydrochloride CAS#: 1137868-52-0 Chemical Formula: C27H36Cl2F3N7O3 Exact Mass: 634.52 | |
| Storage | -20℃ for 3 years in powder form |
| -80℃ for 2 years in solvent | |
| Technical Information | Synonym: TAK-960, TAK960 dihydrochloride, TAK 960 dihydrochloride Chemical Name: 4-((9-cyclopentyl-7,7-difluoro-5-methyl-6-oxo-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b][1,4]diazepin-2-yl)amino)-2-fluoro-5-methoxy-N-(1-methylpiperidin-4-yl)benzamide dihydrochloride SMILES Code: 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 |
| Target | 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) |
|---|---|
| In Vitro | 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]. |
| In Vivo | 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]. |
| Kinase Assay | 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 Assay | 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 Admin | 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. [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. |
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