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PHA-665752
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。
PHA-665752图片
CAS NO:477575-56-7
包装与价格:
包装价格(元)
10 mM * 1 mL in DMSO电议
5mg电议
10mg电议
25mg电议
50mg电议
100mg电议
200mg电议
500mg电议

产品介绍
PHA-665752 是一种选择性的 ATP 竞争活性位点c-Met激酶抑制剂,Ki为 4 nM,IC50为 9 nM。PHA-665752 对 c-Met 的选择性比一组不同的酪氨酸和丝氨酸苏氨酸激酶高 50 倍。PHA-665752 诱导细胞凋亡和细胞周期阻滞,具有细胞还原性抗肿瘤活性。
生物活性

PHA-665752 is a selective, ATP-competitive, and active-site inhibitor of the catalytic activity ofc-Metkinase (Ki=4 nM;IC50=9 nM). PHA-665752 exhibits >50-fold selectivity for c-Met compared with a panel of diverse tyrosine and serine-threonine kinases. PHA-665752 inducesapoptosisand cell cycle arrest, and exhibits cytoreductive antitumor activity[1][2].

IC50& Target

Ki: 4 nM[1]
IC50: 9 nM (c-Met)[1]

体外研究
(In Vitro)

PHA-665752 is a potent and ATP-competitive inhibitor of c-Met kinase activity with a Kiof 4 nM and an IC50of 9 nM[1].
PHA-665752 exhibits >50-fold selectivity for c-Met enzyme compared with the majority of kinases evaluated[1].
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)[1].
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[1].
PHA-665752 (0-1.25 μM; 18 hours) potently inhibits HGF and c-Met-driven phenotypes such as cell growth (proliferation and survival), cell motility, invasion, and/or morphology of a variety of tumor cells[1].
PHA-665752 (0-1.25 μM; 72 hours) induces apoptosis in both the presence and absence of HGF at concentrations that inhibited tyrosine phosphorylation of c-Met in GTL-16 cells[1].
PHA-665752 (0.0125-0.2 μM; 4 hours) potent inhibits HGF-induced c-Met phosphorylation in A549 cells[1].

Cell Proliferation Assay[1]

Cell Line:S114 cells, GTL-16 cells, NCI-H441 cells, or BxPC-3 cells
Concentration:0 μM, 0.002 μM, 0.01 μM, 0.05 μM, 0.25 μM, 1.25 μM
Incubation Time:18 hours
Result:Potently inhibited HGF and c-Met-driven cell growth.

Apoptosis Analysis[1]

Cell Line:GTL-16 cells
Concentration:0 μM, 0.002 μM, 0.01 μM, 0.05 μM, 0.25 μM, 1.25 μM
Incubation Time:72 hours
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.

Western Blot Analysis[1]

Cell Line:A549 cells
Concentration:0.0125 μM, 0.025 μM,0.05 μM,0.1 μM,0.2 μM
Incubation Time:4 hours
Result:Potent inhibited HGF-induced c-Met phosphorylation in A549 cells.
体内研究
(In Vivo)

PHA-665752 (7.5-30 mg/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 30 mg/kg/day, 15 mg/kg/day, and 7.5 mg/kg/day doses, respectively[1].
PHA-665752 shows a potent cytoreductive activity in a gastric carcinoma xenograft model[1].

Animal Model:Female athymic mice (nu/nu, 8–12 weeks) bearing S114 or GTL-16 tumor xenografts[1]
Dosage:7.5 mg/kg/day, 15 mg/kg/day, 30 mg/kg/day
Administration:Intravenous injection; for 9 days
Result:Demonstrated statistically significant dose-dependent tumor growth inhibition.
分子量

641.61

性状

Solid

Formula

C32H34Cl2N4O4S

CAS 号

477575-56-7

运输条件

Room temperature in continental US; may vary elsewhere.

储存方式
Powder-20°C3 years
4°C2 years
In solvent-80°C6 months
-20°C1 month
溶解性数据
In Vitro: 

DMSO : 25 mg/mL(38.96 mM;Need ultrasonic)

配制储备液
浓度溶剂体积质量1 mg5 mg10 mg
1 mM1.5586 mL7.7929 mL15.5858 mL
5 mM0.3117 mL1.5586 mL3.1172 mL
10 mM0.1559 mL0.7793 mL1.5586 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。-80℃ 储存时,请在 6 个月内使用,-20℃ 储存时,请在 1 个月内使用。

In Vivo:

请根据您的实验动物和给药方式选择适当的溶解方案。以下溶解方案都请先按照In Vitro方式配制澄清的储备液,再依次添加助溶剂:

——为保证实验结果的可靠性,澄清的储备液可以根据储存条件,适当保存;体内实验的工作液,建议您现用现配,当天使用; 以下溶剂前显示的百
分比是指该溶剂在您配制终溶液中的体积占比;如在配制过程中出现沉淀、析出现象,可以通过加热和/或超声的方式助溶

  • 1.

    请依序添加每种溶剂: 10% DMSO    40%PEG300   5%Tween-80   45% saline

    Solubility: ≥ 2.5 mg/mL (3.90 mM); Clear solution

    此方案可获得 ≥ 2.5 mg/mL (3.90 mM,饱和度未知) 的澄清溶液。

    以 1 mL 工作液为例,取 100 μL 25.0 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中,混合均匀;向上述体系中加入50 μL Tween-80,混合均匀;然后继续加入 450 μL生理盐水定容至 1 mL。

    将 0.9 g 氯化钠,完全溶解于 100 mL ddH2O 中,得到澄清透明的生理盐水溶液
  • 2.

    请依序添加每种溶剂: 10% DMSO    90% (20%SBE-β-CDin saline)

    Solubility: 2.5 mg/mL (3.90 mM); Suspended solution; Need ultrasonic

    此方案可获得 2.5 mg/mL (3.90 mM) 的均匀悬浊液,悬浊液可用于口服和腹腔注射。

    以 1 mL 工作液为例,取 100 μL 25.0 mg/mL 的澄清 DMSO 储备液加到 900 μL20% 的 SBE-β-CD 生理盐水水溶液中,混合均匀。

    将 2 g 磺丁基醚 β-环糊精加入 5 mL 生理盐水中,再用生理盐水定容至 10 mL,完全溶解,澄清透明
  • 3.

    请依序添加每种溶剂: 10% DMSO    90%corn oil

    Solubility: ≥ 2.5 mg/mL (3.90 mM); Clear solution

    此方案可获得 ≥ 2.5 mg/mL (3.90 mM,饱和度未知) 的澄清溶液,此方案不适用于实验周期在半个月以上的实验。

    以 1 mL 工作液为例,取 100 μL 25.0 mg/mL 的澄清 DMSO 储备液加到 900 μL玉米油中,混合均匀。

*以上所有助溶剂都可在本网站选购。