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Crizotinib
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。
Crizotinib图片
CAS NO:877399-52-5
包装与价格:
包装价格(元)
10 mM * 1 mL in DMSO电议
10mg电议
50mg电议
100mg电议
200mg电议
500mg电议
1 g电议
5 g电议

产品名称
克唑替尼
PF-02341066
产品介绍
Crizotinib (PF-02341066) 是一种具有口服活性的,ATP 竞争性的ALKc-Met抑制剂,IC50分别为 20 和 8 nM。在细胞的实验中,Crizotinib 抑制 NPM-ALK 的酪氨酸磷酸化和 c-Met 的酪氨酸磷酸化,IC50分别为 24 和 11 nM。Crizotinib 也是ROS1抑制剂。Crizotinib 具有有效的肿瘤生长抑制作用。
生物活性

Crizotinib (PF-02341066) is an orally bioavailable, ATP-competitiveALKandc-Metinhibitor withIC50s of 20 and 8 nM, respectively. Crizotinib inhibits tyrosine phosphorylation of NPM-ALK and tyrosine phosphorylation of c-Met with IC50s of 24 and 11 nM in cell-based assays, respectively. Crizotinib is also aROS1inhibitor. Crizotinib has effective tumor growth inhibition[1][2][3].

IC50& Target

IC50: 20 nM (ALK), 8 nM (c-Met)[3]

体外研究
(In Vitro)

Crizotinib (PF-02341066) displays similar potency against c-Met phosphorylation in mIMCD3 mouse or MDCK canine epithelial cells with IC50of 5 nM and 20 nM, respectivly. PF-2341066 shows improved or similar activity against NIH3T3 cells engineered to express c-Met ATP-binding site mutants V1092I or H1094R or the P-loop mutant M1250T with IC50of 19 nM, 2 nM and 15 nM, respectively, compared with NIH3T3 cells expressing wild-type receptor with IC50of 13 nM. In contrast, a marked shift in potency of PF-2341066 is observed against cells engineered to express c-Met activation loop mutants Y1230C and Y1235D with IC50of 127 nM and 92 nM, respectively, compared with wild-type receptor. PF-2341066 also potently prevents the phosphorylation of c-Met in NCI-H69 and HOP92 cells, with IC50of 13 nM and 16 nM, respectively, which express the endogenous c-Met variants R988C and T1010I, respectively[1].
Crizotinib (PF-02341066) also potently inhibits NPM-ALK phosphorylation in Karpas299 or SU-DHL-1 ALCL cells with an IC50of 24 nM. PF-2341066 potently prevents cell proliferation, which is associated with G(1)-S-phase cell cycle arrest and induction of apoptosis in ALK-positive ALCL cells with IC50of 30 nM, but not ALK-negative lymphoma cells[2].

体内研究
(In Vivo)

Crizotinib (PF-02341066) reveals the ability to cause marked regression of large established tumors (>600 mm3) in both the 50 mg/kg/day and 75 mg/kg/day treatment cohorts, with a 60% decrease in mean tumor volume over the 43-day administration schedule in the GTL-16 model. In an another study, PF-2341066 displays the ability to completely inhibits GTL-16 tumor growth for >3 months, with only 1 of 12 mice exhibiting a significant increase in tumor growth over the 3-month treatment schedule at 50 mg/kg/day. A significant dose-dependent reduction of CD31-positive endothelial cells is observed at 12.5 mg/kg/day, 25 mg/kg/day, and 50 mg/kg/day in GTL-16 tumors, indicating that inhibition of MVD shows a dose-dependent correlation to antitumor efficacy. PF-2341066 displays a significant dose-dependent reduction of human VEGFA and IL-8 plasma levels in both the GTL-16 and U87MG models. Marked inhibition of phosphorylated c-Met, Akt, Erk, PLCλ1, and STAT5 levels is observed in GTL-16 tumors following p.o. administration of PF-2341066[1].
Treatment of c-MET-amplified GTL-16 xenografts with 50 mg/kg PF-2341066 elicits tumor regression that is associated with a slow reduction in 18F-FDG uptake and decreases expression of the glucose transporter 1, GLUT-1[4].

Clinical Trial
分子量

450.34

性状

Solid

Formula

C21H22Cl2FN5O

CAS 号

877399-52-5

中文名称

克唑替尼;可唑替尼;克卓替尼;克唑替尼;克里唑替尼

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 : 33.33 mg/mL(74.01 mM;Need ultrasonic)

H2O :< 0.1 mg/mL (ultrasonic)(insoluble)

配制储备液
浓度溶剂体积质量1 mg5 mg10 mg
1 mM2.2205 mL11.1027 mL22.2054 mL
5 mM0.4441 mL2.2205 mL4.4411 mL
10 mM0.2221 mL1.1103 mL2.2205 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: ≥ 1.25 mg/mL (2.78 mM); Clear solution

    此方案可获得 ≥ 1.25 mg/mL (2.78 mM,饱和度未知) 的澄清溶液。

    以 1 mL 工作液为例,取 100 μL 12.5 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: ≥ 1.25 mg/mL (2.78 mM); Clear solution

    此方案可获得 ≥ 1.25 mg/mL (2.78 mM,饱和度未知) 的澄清溶液。

    以 1 mL 工作液为例,取 100 μL 12.5 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: ≥ 1.25 mg/mL (2.78 mM); Clear solution

    此方案可获得 ≥ 1.25 mg/mL (2.78 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 12.5 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。