| 中文名称: | PHA-665752 | ||||
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| 英文名称: | PHA-665752 | ||||
| 别名: | (2R)-1-[[5-[(Z)-[5-[[(2,6-二氯苯基)甲基]磺酰]-1,2-二氢-2-氧代-3H-吲哚-3-亚基]甲基]-2,4-二甲基-1H-吡咯-3-基]羰基]-2-(1-吡咯烷甲基)吡咯烷 (2R)-1-[[5-[(Z)-[5-[[(2,6-DICHLOROPHENYL)METHYL]SULFONYL]-1,2-DIHYDRO-2-OXO-3H-INDOL-3-YLIDENE]METHYL]-2,4-DIMETHYL-1H-PYRROL-3-YL]CARBONYL]-2-(1-PYRROLIDINYLMETHYL)PYRROLIDINE | ||||
| CAS No: | 477575-56-7 | 分子式: | C32H34Cl2N4O4S | 分子量: | 641.61 |
| CAS No: | 477575-56-7 | ||||
| 分子式: | C32H34Cl2N4O4S | ||||
| 分子量: | 641.61 | ||||
基本信息
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产品编号：P10801 |
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产品名称：PHA-665752 |
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CAS: |
477575-56-7 |
储存条件 |
粉末 |
-20℃ |
四年 |
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分子式： |
溶于液体 |
-80℃ |
六个月 |
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分子量 |
641.61 |
-20℃ |
一个月 |
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化学名： |
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Solubility (25°C) |
体外 |
DMSO |
128mg/mL (199.49mM) |
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Ethanol |
Insoluble |
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Water |
Insoluble |
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体内（现配现用） |
2% DMSO+castor oil |
5mg/mL |
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＜1mg/ml表示微溶或不溶。 |
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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。 |
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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。 |
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制备储备液
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浓度
溶液体积 质量 |
1mg |
5mg |
10mg |
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1mM |
1.5586mL |
7.7929mL |
15.5858mL |
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5mM |
0.3117mL |
1.5586mL |
3.1172mL |
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10mM |
0.1559mL |
0.7793mL |
1.5586mL |
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50mM |
0.031mL |
0.1559mL |
0.3117mL |
生物活性
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产品描述 |
一种选择性的 ATP 竞争活性位点 c-Met 激酶抑制剂，Ki 为 4nM，IC50为 9nM。 |
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靶点/IC50 |
Ki: 4nM IC50: 9nM (c-Met) |
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体外研究 |
PHA-665752 is a potent and ATP-competitive inhibitor of c-Met kinase activity with a Ki of 4nM and an IC50 of 9 nM.PHA-665752 exhibits >50-fold selectivity for c-Met enzyme compared with the majority of kinases evaluated.PHA-665752 shows potent inhibition of c-Met RTK autophosphorylation in NIH3T3 cells engineered to express high levels of c-Met and hepatocyte growth factor (HGF).PHA-665752 inhibits HGF-stimulated or constitutive phosphorylation of mediators of downstream of c-Met such as Gab-1,ERK, Akt, STAT3, PLC-γ, and FAK in multiple tumor cell lines.PHA-665752 (0-1.25μM; 18 hours) potently inhibits HGF and Met-driven phenotypes such as cell growth (proliferation and survival), cell motility, invasion, and/or morphology of a variety of tumor cells.PHA-665752 (0-1.25μM; 72 hours) induces apoptosis in both the presence and absence of HGF at concentrations that nhibited tyrosine phosphorylation of c-Met in GTL-16 cells.PHA-665752 (0.0125-0.2 μM; 4 hours) potent inhibits HGF-induced c-Met phosphorylation in A549 cells. |
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Cell Line: |
S114 cells, GTL-16 cells, NCI-H441 cells, or BxPC-3 cells |
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Concentration: |
0 μM,0.002μM,0.01μM,0.05μM,0.25μM, 1.25μM |
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Incubation Time: |
18 hours |
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Result: |
Potently inhibited HGF and c-Met-driven cell growth. |
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Apoptosis Analysis |
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Cell Line: |
GTL-16 cells |
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Concentration: |
0μM,0.002μM,0.01μM,0.05μM,0.25μM,1.25μM |
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Incubation Time: |
72 hours |
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Result: |
Induced apoptosis in both the presence and absence of HGF at concentrations that inhibited tyrosine phosphorylation of c-Met in GTL-16 cells. Immunoblot Analysis. |
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Western Blot Analysis |
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Cell Line: |
A549 cells |
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Concentration: |
0.0125μM,0.025μM,0.05μM,0.1μM,0.2μM |
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Incubation Time: |
4 hours |
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Result: |
Potent inhibited HGF-induced c-Met phosphorylation in A549 cells. |
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体内研究 |
PHA-665752 (7.5-30mg/kg/day; i.v. ; for 9 days) exhibits statistically significant dose-dependent tumor growth inhibition of 68%, 39%, and 20% of vehicle control at the 30mg/kg/day,15mg/kg/day, and 7.5mg/kg/day doses,respectively.PHA-665752 shows a potent cytoreductive activity in a gastric carcinoma xenograft model. |
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Animal Model: |
Female athymic mice (nu/nu, 8–12 weeks) bearing S114 or GTL-16 tumor xenografts |
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Dosage: |
7.5mg/kg/day, 15mg/kg/day, 30mg/kg/day |
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Administration: |
Intravenous injection; for 9 days |
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Result: |
Demonstrated statistically significant dose-dependent tumor growth inhibition. |
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推荐实验方法(仅供参考)
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激酶实验： |
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体外酶实验 |
使用GST融合蛋白的c-Met激酶域进行c-Met实验。在ATP和二价阳离子 (MgCl2 或 MnCl2 10-20mM)存在时，根据激酶肽底物和聚-glu-tyr的磷酸化，测定PHA-665752抑制c-Met的IC50值。测定作用于c-Met的线性范围(即,速率维持初始速率的时间周期), 然后在这个范围内测定动力学和IC50值。 |
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细胞实验: |
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细胞系 |
S114, GTL-16, NCI-H441, 和 BxPC-3 |
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浓度 |
溶于DMSO, 终浓度为~10μM |
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处理时间 |
18,或72小时 |
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方法 |
增殖实验中, 细胞生长在含0.1% FBS 的培养基中48小时， 然后使用不同浓度PHA-665752处理细胞。18小时后,细胞和BrdUrd温育1小时，混合，使用抗BrdUrd过氧化物酶抗体染色,然后实验板在630nm处读数。凋亡实验中, 细胞生长在含2% FBS的培养基中，在有或无HGF (50ng/mL) 存在时，使用不同浓度PHA-665752处理细胞72小时。72小时后, 加入含溴化乙锭和吖啶橙的混合物,通过荧光显微镜计算凋亡细胞(明亮的橙色细胞或细胞碎片)。 |
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动物实验: |
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动物模型 |
携带S114 或GTL-16移植瘤的雌性无胸腺nu/nu小鼠 |
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剂量 |
~30mg/kg/day |
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给药处理 |
静脉注射 |
本计算器可帮助您计算出特定溶液中溶质的质量、溶液浓度和体积之间的关系，公式为：
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
用本工具协助配置特定浓度的溶液，使用的计算公式为：
开始浓度 x 开始体积 = 最终浓度 x 最终体积
稀释公式
稀释公式一般简略地表示为：C1V1 = C2V2 ( 输入 输出 )
