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TAK-960 dihydrochloride
本产品不向个人销售,仅用作科学研究,不用于任何人体实验及非科研性质的动物实验。
TAK-960 dihydrochloride图片
包装与价格:
包装价格(元)
Free Sample (0.1-0.5mg)电议
10mM (in 1mL DMSO)电议
5mg电议
10mg电议
50mg电议
100mg电议
200mg电议
500mg电议

产品介绍
TAK-960 dihydrochloride 是一种有效的,可口服的,选择性的 polo-like kinase 1 (PLK1) 抑制剂,在 10 μM ATP 的条件下,IC50 值为 0.8 nM;TAK-960 dihydrochloride 同时对 PLK2 和 PLK3 也有抑制作用,IC50 值分别为 16.9 和 50.2 nM。

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.

产品描述

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.