TAK-960 dihydrochloride

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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 是一种有效的，可口服的，选择性的polo-like kinase 1 (PLK1)抑制剂，IC₅₀为 0.8 nM。TAK-960 dihydrochloride 对 PLK2 和 PLK3 也有抑制作用，IC₅₀分别为 16.9 和 50.2 nM。TAK-960 dihydrochloride 抑制多种肿瘤细胞系的增殖，对多种肿瘤异种移植具有显著的疗效。

生物活性

TAK-960 dihydrochloride is an orally available, selective inhibitor ofpolo-like kinase1 (PLK1), with anIC₅₀of 0.8 nM. TAK-960 dihydrochloride also shows inhibitory activities againstPLK2andPLK3, with IC₅₀s of 16.9 and 50.2 nM, respectively. TAK-960 dihydrochloride inhibits proliferation of multiplecancercell lines and exhibits significant efficacy against multiple tumor xenografts^[1].

IC₅₀& Target^[1]

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)

体外研究
(In Vitro)

TAK-960 dihydrochloride treatment causes accumulation of G2-M cells, aberrant polo mitosis morphology, and increased phosphorylation of histone H3 (pHH3). TAK-960 dihydrochloride (2-1000 nM; 72 hours) inhibits proliferation of multiple cancer cell lines, with mean EC₅₀values ranging from 8.4 to 46.9 nM, but not in nondividing normal cells^[1].
TAK-960 dihydrochloride (8 nM) leads to G2/M cell cycle arrest without significant cytotoxicity in HeLa cells^[2].

Cell Viability Assay^[1]

Cell Line:	HT-29, HCT116, COLO320DM, HCT-15, RKO, SW480, K-562….Hela, DU 145 cells
Concentration:	2-1000 nM
Incubation Time:	72 hours
Result:	Inhibited proliferation of human cancer cell lines regardless of TP53 and KRAS mutation and MDR1 expression status.

体内研究
(In Vivo)

TAK-960 dihydrochloride exhibits (10 mg/kg; p.o.; once daily for 2 weeks) significant efficacy against multiple tumor xenografts^[1].
In animal models, TAK-960 dihydrochloride (p.o.) increases pHH3 in a dose-dependent manner and significantly inhibits the growth of HT-29 colorectal cancer xenografts^[1].

Animal Model:	nude mice or SCID mice (bearing HCT116, PC-3, BT474, A549, NCI-H1299, NCI-H1975, A2780, and MV4-11 cells)^[1]
Dosage:	10 mg/kg
Administration:	P.o.; once daily for 2 weeks
Result:	Substantial antitumor activity and good tolerability.

Clinical Trial

分子量

634.52

性状

Solid

Formula

C₂₇H₃₆Cl₂F₃N₇O₃

运输条件

Room temperature in continental US; may vary elsewhere.

储存方式

4°C, sealed storage, away from moisture

*In solvent : -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture)

溶解性数据

In Vitro:

H₂O : 10 mg/mL(15.76 mM;Need ultrasonic)

DMSO : 3.23 mg/mL(5.09 mM;Need ultrasonic)

配制储备液

浓度溶剂体积质量

1 mg

5 mg

10 mg

1 mM	1.5760 mL	7.8800 mL	15.7599 mL
5 mM	0.3152 mL	1.5760 mL	3.1520 mL
10 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；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。
储备液的保存方式和期限：-80℃, 6 months; -20℃, 1 month (sealed storage, away from moisture)。-80℃ 储存时，请在 6 个月内使用，-20℃ 储存时，请在 1 个月内使用。