NVP-TNKS656

製品コードS7238 バッチS723802

化学情報

	Synonyms	N/A	Storage (From the date of receipt)	3 years -20°C powder 1 years -80°C in solvent
	化学式	C₂₇H₃₄N₄O₅
	分子量	494.58	CAS No.	1419949-20-4
Solubility (25°C)*	体外	DMSO	100 mg/mL (202.19 mM)
		Ethanol	10 mg/mL warmed with 50ºC water bath (20.21 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	NVP-TNKS656 is a highly potent, selective, and orally active tankyrase inhibitor with IC50 of 6 nM for TNKS2, > 300-fold selectivity against PARP1 and PARP2.
in vitro	In vitro, NVP-TNKS656 shows low to moderate microsomal ER values across species and high solubility. ^[1] In PI3K or AKT inhibitor-resistant cells, NVP-TNKS656 blocks Wnt/β-Catenin pathway and promotes apoptosis. ^[2]
in vivo	In mice, NVP-TNKS656 displays low clearance and volume of distribution, and exhibits good exposure and moderate oral bioavailability. In MMTV-Wnt1 tumor bearing athymic nude mice, NVP-TNKS656 (350 mg/kg, p.o.) stabilizes Axin1 protein and reduces the Wnt/beta-catenin target gene Axin2 mRNA level by 70-80%. ^[1] In colorectal cancer PDX models, NVP-TNKS656 reduces nuclear β-catenin, reverts such resistance, and represses tumor growth. ^[2]

製品説明

NVP-TNKS656 is a highly potent, selective, and orally active tankyrase inhibitor with IC50 of 6 nM for TNKS2, > 300-fold selectivity against PARP1 and PARP2.

in vitro

In vitro, NVP-TNKS656 shows low to moderate microsomal ER values across species and high solubility. ^[1]

In PI3K or AKT inhibitor-resistant cells, NVP-TNKS656 blocks Wnt/β-Catenin pathway and promotes apoptosis. ^[2]

in vivo

In mice, NVP-TNKS656 displays low clearance and volume of distribution, and exhibits good exposure and moderate oral bioavailability. In MMTV-Wnt1 tumor bearing athymic nude mice, NVP-TNKS656 (350 mg/kg, p.o.) stabilizes Axin1 protein and reduces the Wnt/beta-catenin target gene Axin2 mRNA level by 70-80%. ^[1]

In colorectal cancer PDX models, NVP-TNKS656 reduces nuclear β-catenin, reverts such resistance, and represses tumor growth. ^[2]

プロトコル(参考用のみ)

キナーゼアッセイ	Tankyrase AutoPARsylation Assay
キナーゼアッセイ	PARP catalytic activity is monitored using the quantitative liquid chromatography/mass spectrometry (LC-MS) detection of nicotinamide. The autoPARsylation reactions are performed at room temperature in 384-well Greiner flat-bottom plates. The final reaction mixture contains 2.5% DMSO and inhibitors with concentrations ranging from 0.0001 to 18.75 μM. GST-TNKS2P, GST-TNKS1P, PARP1, and PARP2 enzymes are used at final concentrations or 5, 5, 5, and 2 nM, respectively. The nicotinamide concentration in the resulting supernatants is measured by LC-MS. The % inhibition is calculated as follows: (control – sample)/(control – background) × 100. “Control” is the average value of eight wells without compound, and “background” is the average of eight wells mixed with 5× quenching solution measured prior to initiation of the reaction.
細胞アッセイ	細胞株	Cell-free assays
	濃度	6 nM
	反応時間
	実験の流れ
動物実験	動物モデル	Athymic female nude mice bearing MMTV-Wnt1 tumors
	投薬量	350 mg/kg
	投与方法	p.o.

参考

Selleckの高級品が、幾つかの出版された研究調査結果（以下を含む）で使われた：

Systematic mapping and modeling of 3D enhancer-promoter interactions in early mouse embryonic lineages reveal regulatory principles that determine the levels and cell-type specificity of gene expression [ bioRxiv, 2023, 2023.07.19.549714]	PubMed: 37577543
Systematic mapping and modeling of 3D enhancer-promoter interactions in early mouse embryonic lineages reveal regulatory principles that determine the levels and cell-type specificity of gene expression [ bioRxiv, 2023, 2023.07.19.549714]	PubMed: 37577543
Identification of novel target for osteosarcoma by network analysis [ Med Sci Monit, 2018, 24: 5914–5924]	PubMed: 30144309
Identification of Novel Target for Osteosarcoma by Network Analysis [Zhi LQ, et al. Med Sci Monit, 2018, 24:5914-5924]	PubMed: 30144309

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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