TAK-960-dihydrochloride - Polo-like Kinase (PLK) 抑制剂 - 生命科学试剂 - MedChemExpress

1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemETAK-960 dihydrochlorideCat. No.: HY-15160B分式: CHClFNO分量: 634.52作靶点: Polo-like Kinase (PLK)作通路: Cell Cycle/DNA Damage储存式: Powder -20C 3 years4C 2 yearsIn solvent -80C 6 months-20C 1 month溶解性数据体外实验 DMSO : 98.57 mg/mL (155.35 mM)*

2、means soluble, but saturation unknown.Mass Solvent1 mg 5 mg 10 mg Concentration制备储备液1 mM 1.5760 mL 7.8800 mL 15.7599 mL5 mM 0.3152 mL 1.5760 mL 3.1520 mL10 mM 0.1576 mL 0.7880 mL 1.5760 mL请根据产品在不同溶剂中的溶解度，选择合适的溶剂配制储备液，并请注意储备液的保存式和期限。BIOLOGICAL ACTIVITY物活性 TAK-960 dihydrochloride种有效的，可服的，选择性的 polo-lik

3、e kinase 1 (PLK1) 抑制剂，在 10 MATP 的条件下，IC50 值为 0.8 nM；TAK-960 dihydrochloride 同时对 PLK2 和 PLK3 也有抑制作，IC50 值分别为 16.9 和 50.2 nM。IC50 & Target PLK1 PLK2 PLK3 FAK/PTK20.8 nM (IC50) 16.9 nM (IC50) 50.2 nM (IC50) 19.6 nM (IC50)MLCK/MYLK FES/FPS1/3 Master of Small Molecules 您边的抑制剂师www.MedChemE25.6 nM (IC50) 5

4、8.2 nM (IC50)体外研究 TAK-960 inhibits full-length PLK1 protein with IC50 of 0.8 nM, wich is 20-fold lower than the next lowest IC50value (PLK2: 16.9 nM). TAK-960 (2-1000 nM) causes accumulation of G2-M cells in HT-29 cells. TAK-960inhibits proliferation of multiple cancer cell lines, with mean EC50 val

5、ues ranging from 8.4 to 46.9 nM, but notin nondividing normal cells 1. TAK-960 (8nM) leads to G2/M cell cycle arrest without significant cytotoxicityin HeLa cells. TAK-960 does not sensitize cancer cells to radiation when an insufficient amount of time isprovided to induce mitotic arrest. The overex

6、pression of a PLK1 mutant, PLK1-R136G&T210D, which isconfirmed to cancel the TAK-960-mediated increase in the proportion of mitotic cells, abrogates theradiosensitizing effects of TAK-960 2.体内研究 TAK-960 (7.5 mg/kg, p.o.) shows a significant increase in median survival compared with vehicle in MV4-11

7、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 (10mg/kg) significantly suppresses tumor growth whencombined with IR in tumor xenografts 2.PROTOCOLKinase Assay 1 The inhibitory activity of TAK-960 is asse

8、ssed by the TR-FRET (fluorescence resonance energy transfer)assay, which measures the ATP-dependent phosphorylation of a biotinylated substrate peptidecorresponding to residues 2,470 through 2,488 of the mTOR protein (Biotin-AGAGTVPESIHSFIGDGLV). Atotal of 288 kinases are screened for TAK-960 inhibi

9、tion (1 M) using HotSpot technology and IC50 valuesfor the selected kinases are determined.MCE has not independently confirmed the accuracy of these methods. They are for reference only.Cell Assay 1 Cells are seeded into 96-well plates at 3,000 to 30,000 cells per well in appropriate medium plus 10%

10、 fetalcalf serum. After 24 hours, cells are treated with serial dilutions of TAK-960, and 72 hours later, the numberof viable cells is assessed using the CellTiter-Glo Assay. Calculation of EC50 values and statistical analysisare done using GraphPad Prism software.MCE has not independently confirmed

11、 the accuracy of these methods. They are for reference only.Animal The suspension of HeLa cells (2106 in 100L PBS) or H1299 cells (3106 in 100L PBS) isAdministration 2 subcutaneously inoculated into the right hind legs of 8-week-old nude mice (BALB/c nu/nu mice). Theindicated dose of TAK-960 is oral

12、ly administered to tumor-bearing mice. In the radiation treatment, tumorxenografts are locally irradiated with the indicated dose of 137Cs -rays using a Gammacell 40 Exactor.MCE has not independently confirmed the accuracy of these methods. They are for reference only.户使本产品发表的科研献 Sci Transl Med. 201

13、8 Jul 18;10(450). pii: eaaq1093.See more customer validations on HYPERLINK / www.MedChemEREFERENCES2/3 Master of Small Molecules 您边的抑制剂师www.MedChemE1. Hikichi Y, et al. TAK-960, a novel, orally available, selective inhibitor of polo-like kinase 1, shows broad-spectrum preclinical antitumoractivity 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. 2015Oct 27;5:15