TAK-960

製品コードS1239 バッチS123901

化学情報

	Synonyms		Storage (From the date of receipt)	3 years -20°C powder 1 years -80°C in solvent
	化学式	C₂₇H₃₄F₃N₇O₃
	分子量	561.6	CAS No.	1137868-52-0
Solubility (25°C)*	体外	DMSO	13 mg/mL (23.14 mM)
		Ethanol	3 mg/mL (5.34 mM)
		Water	Insoluble
* <1 mg/ml means slightly soluble or insoluble. * Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.

溶剤液（一定の濃度）を調合する

生物活性

製品説明	TAK-960 is a novel, investigational, orally bioavailable, potent, and selective PLK1 inhibitor that has shown activity in several tumor cell lines, including those that express multidrug-resistant protein 1 (MDR1).
in vitro	TAK-960 has shown activity in several tumor cell lines including those that express multidrug resistant protein 1 (MDR1). ^[1] Consistent with PLK1 inhibition, TAK-960 treatment gives rise to accumulation of G2/M cells, aberrant "polo" mitosis morphology, and increases phosphorylation of histone H3 (pHH3). ^[1] TAK-960 inhibits proliferation of multiple cancer cell lines, with mean EC50 values ranging from 8.4 to 46.9 nM, but not in non-dividing normal cells (EC50 >1,000 nM). The mutation status of TP53 or KRAS and MDR1 expression does not correlate with the potency of TAK-960 in the cell lines tested. ^[1]
in vivo	In animal models, oral administration of TAK-960 increases pHH3 in a dose-dependent manner and significantly inhibits the growth of HT-29 colorectal cancer xenografts. ^[1] Treatment with once-daily TAK-960 exhibits significant efficacy against multiple tumor xenografts, including an Doxorubicin/Paclitaxel-resistant xenograft model and a disseminated leukemia model. ^[1]
特徴	The discovery of TAK -960 provides an interesting example of how the addition of fluorine atoms during optimization significantly alters the attributes of the leads series.

プロトコル(参考用のみ)

キナーゼアッセイ	Biochemical kinase inhibition assays
キナーゼアッセイ	The inhibitory activity of TAK-960 is assessed by the TR-FRET assay, which measures the ATP-dependent phosphorylation of a biotinylated substrate peptide corresponding to residues 2470 through 2488 of the mammalian target of rapamycin protein (Biotin-AGAGTVPESIHSFIGDGLV). A total of 288 kinases are screened for TAK-960 inhibition (1 μM) using HotSpot^SM technology and IC50 values for the selected kinases are determined.
細胞アッセイ	細胞株	Human tumor cell lines including those with TP53 or KRAS mutations or MDR1 overexpression
	濃度	0.001-1μM
	反応時間	72 hours
	実験の流れ	Cells are seeded into 96-well plates at 3-30 × 10³ cells/well in appropriate medium plus 10% fetal calf serum (FCS). 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.
動物実験	動物モデル	Athymic nude mice (BALB/cAJc1-nu/nu), severe combined immunodeficiency (SCID) mice (C.B17-Icr- scid/scid Jcl) or NOD-scid mice (NOD.CB17-Prkdc scid/J)
	投薬量	30 mg/kg
	投与方法	Oral dosing

参考

[1] Hikichi Y, et al. Mol Cancer Ther, 2012, 11(3), 700-709.

長期の保管のために-20°Cの下で製品を保ってください。

人間や獣医の診断であるか治療的な使用のためにでない。

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