1-(4-((4-Ethylpiperazin-1-yl)methyl)-3-(trifluoromethyl)phenyl)-3-(4-((6-(methylamino)pyrimidin-4-yl)oxy)phenyl)urea - CAS:630124-46-8

中文名称:	1-(4-((4-Ethylpiperazin-1-yl)methyl)-3-(trifluoromethyl)phenyl)-3-(4-((6-(methylamino)pyrimidin-4-yl)oxy)phenyl)urea
英文名称:	1-(4-((4-Ethylpiperazin-1-yl)methyl)-3-(trifluoromethyl)phenyl)-3-(4-((6-(methylamino)pyrimidin-4-yl)oxy)phenyl)urea
别名:	1-(4-((4-Ethylpiperazin-1-yl)methyl)-3-(trifluoromethyl)phenyl)-3-(4-((6-(methylamino)pyrimidin-4-yl)oxy)phenyl)urea AST 487；NVP-AST 487
CAS No:	630124-46-8	分子式:	C₂₆H₃₀F₃N₇O₂	分子量:	529.56
CAS No:	630124-46-8
分子式:	C₂₆H₃₀F₃N₇O₂
分子量:	529.56

安全技术说明书(PDF) MSDS(PDF) 点击下载产品说明书(PDF)

A12614 1-(4-((4-Ethylpiperazin-1-yl)methyl)-3-(trifluoromethyl)phenyl)-3-(4-((6-(methylamino)pyrimidin-4-yl)oxy)phenyl)urea ≥98% (psaitong)

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包装规格：

5mg 10mg 50mg in glass bottle

溶解性：

溶于DMSO（≥100mg/mL）

产品描述：

基本信息

产品编号：A12614
产品名称：1-(4-((4-Ethylpiperazin-1-yl)methyl)-3-(trifluoromethyl)phenyl)-3-(4-((6-(methylamino)pyrimidin-4-yl)oxy)phenyl)urea
CAS:	630124-46-8	储存条件	粉末	-20℃	四年

分子式：	C26H30F3N7O2		溶于液体	-80℃	六个月
分子量	529.56			-20℃	一个月
化学名：
Solubility (25°C)	体外	DMSO	100mg/mL (188.83mM)
		Ethanol	33mg/mL (62.31mM)
		Water	Insoluble
	体内（现配现用）
＜1mg/ml表示微溶或不溶。
普西唐提供的所有化合物浓度为内部测试所得，实际溶液度可能与公布值有所偏差，属于正常的批间细微差异现象。
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。

制备储备液

浓度溶液体积质量	1mg	5mg	10mg
1mM	1.8884mL	9.4418mL	18.8836mL
5mM	0.3777mL	1.8884mL	3.7767mL
10mM	0.1888mL	0.9442mL	1.8884mL
50mM	0.0378mL	0.1888mL	0.3777mL

生物活性

产品描述	一种 RET 激酶抑制剂，IC50 为 880 nM，抑制 RET 自磷酸化，及下游效应器激活，也抑制 Flt-3，IC50 为 520 nM。
靶点/IC₅₀	RET	KDR	c-Kit	c-Abl	FLT3 (Cell-free assay)
靶点/IC₅₀					0.12μM(Ki)
体外研究	A number of other kinases are also similarly inhibited by AST 487 (NVP-AST487) in the in vitro kinase assays, including KDR (IC50=170 nM), Flt-4 (IC50=790 nM), Flt-3 (IC50=520 nM), c-Kit (IC50=500 nM), and c-Abl (IC50=20 nM). AST 487 potently inhibits the growth of human thyroid cancer cell lines with activating mutations of RET but not of lines without RET mutations. Both GDNF/GFRα1 and persephin-induced calcitonin mRNA are markedly inhibited by coincubation with 100 nM of AST 487 in MTC-M cells[1]. AST 487 is a novel, mutant FLT3 inhibitor. AST 487 is tested in biochemical assays for inhibition of Flt-3 kinase activity. The Ki is determined to be 0.12 μM. Besides Flt-3, NVP-AST487 inhibits RET, KDR, c-Kit, and c-Abl kinase with IC50 values below 1 μM. Treatment of FLT3-ITD-Ba/F3 cells and D835Y-Ba/F3 cells with AST 487 potently inhibits cellular proliferation (IC5
体内研究	After a single oral administration of 15mg/kg of AST 487 to OF1 mice, a mean peak plasma level (Cmax) of 0.505±0.078μM SE is achieved after 0.5h. Similar levels of AST 487 are found in the plasma of mice up to 6h after oral administration, with a C last of 21±4nM at 24h. The oral bioavailability is calculated to be 9.7% with a t1/2 terminal elimination of 1.5h

推荐实验方法(仅供参考)

激酶实验：

Glutathione S-transferase (GST)-fused kinase domains are expressed in baculovirus and purified over glutathionesepharose. Kinase activity is tested by measuring the phosphorylation of a synthetic substrate [poly(Glu, Tyr)], by purified GST-fusion kinase domains of the respective protein kinase in the presence of radiolabeled ATP; the ATP concentrations used are optimized within the Km range for the individual kinases. Briefly, each kinase is incubated under optimized buffer conditions in 20mM of Tris-HCl (pH 7.5), 1 to 3mM of MnCl2, 3 to 10mM of MgCl2, 10μM of Na3VO4, 1mM of DTT, 0.2μCi [33 P]ATP, 1 to 8μM of ATP, 3 to 8μg/mL of poly(Glu/Tyr, 4:1), and 1% DMSO in a total volume of 30μL in the presence or absence of NVP-AST487 for 10 min at ambient temperature. Reactions are terminated by adding 10μL of 250 mM EDTA, and the reaction mixture is transferred onto an Immobilon polyvinylidene difluoride membrane. Filters are washed (0.5% H3PO4 ), soaked in ethanol, dried and counted in a liquid scintillation counter. IC50s for AST 487 are calculated by linear regression analysis of the percentage inhibition.

细胞实验:

The trypan blue exclusion assay is used to determine proliferation of cells cultured in the presence and absence of NVP-AST 487. Cell viability is reported as percentage of control (untreated) cells, and data are presented as the average of 2 independent experiments, except where indicated. Error bars represent the standard error of the mean for each data point.Apoptosis of drug-treated cells is measured using the Annexin-V-Fluos Staining Kit. Cell-cycle analysis is performed

动物实验:

Mice
Female athymic nude mice are kept under optimized hygienic conditions (maximum of 10 mice per Makrolon type III cage) with free access to food and water. Tumors are established by s.c. injection of 1×106 and 5×106 of NIH3T3-RETC634W and TT cells, respectively, in 100μL of HBSS per mouse. Treatable tumors, i.e., mean tumor volume of 100mm3 , developed within 10 days of NIH3T3-RETC634W cell injection, and within 20 days of TT cell injection. NVP-AST487 is given p.o., once daily by gavage. The compound is formulated by dissolving the appropriate amount of powder in N-methylpyrrolidone/PEG300 (1:10v/v). The mice are randomized into four treatment groups of eight mice each. The first three groups received daily oral administrations of NVP-AST487 at 50, 30, and 10mg/kg, respectively, for 3 weeks. The fourth group received treatment with vehicle. Tumor growth and body weights are monitored twice weekly. Tumor volumes are determined according to the formula: length×diameter2×π/6. Tumors are collected and frozen in liquid nitrogen at the end of the efficacy study, 6 h after the last administration.

保存条件：

-20℃

UN码：

HazardClass：

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安全说明：

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质量 (g) = 浓度 (mol/L) x 体积 (L) x 分子量 (g/mol)

摩尔浓度计算公式

质量 =

浓度 *

体积 *

分子量

*选择对应的单位 *空出希望得到的变量，填写另外两个变量

用本工具协助配置特定浓度的溶液，使用的计算公式为：
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* = *

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初始浓度:
稀释倍数:

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C1=C0/X	C1:	LOG(C1):
C2=C1/X	C2:	LOG(C2):
C3=C2/X	C3:	LOG(C3):
C4=C3/X	C4:	LOG(C4):
C5=C4/X	C5:	LOG(C5):
C6=C5/X	C6:	LOG(C6):
C7=C6/X	C7:	LOG(C7):
C8=C7/X	C8:	LOG(C8):

摩尔浓度计算公式

稀释公式

连续稀释计算器方程

连续稀释

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