Home>>Signaling Pathways>> Tyrosine Kinase>> ROS>>PF-06463922

PF-06463922 Sale

(Synonyms: 劳拉替尼; PF-06463922) 目录号 : GC14794

An orally available inhibitor of ALK and ROS1

PF-06463922 Chemical Structure

Cas No.:1454846-35-5

规格 价格 库存 购买数量
10mM (in 1mL DMSO)
¥620.00
现货
5mg
¥494.00
现货
25mg
¥1,733.00
现货

电话:400-920-5774 Email: sales@glpbio.cn

Customer Reviews

Based on customer reviews.

Sample solution is provided at 25 µL, 10mM.

产品文档

Quality Control & SDS

View current batch:

实验参考方法

Cell experiment [1]:

Cell lines

HCC78 cells harboring the SLC34A2-ROS1(S/L) proteins and BaF3 cells engineered to express the CD74-ROS1 fusion

Preparation method

The solubility of this compound in DMSO is >20.3mg/mL. General tips for obtaining a higher concentration: Please warm the tube at 37℃ for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below -20℃ for several months.

Reacting condition

0-10000 nM

Applications

In HCC78 and BaF3 CD74-ROS1 cells, PF-06463922 potently inhibited cell proliferation with IC50 values of 1.3 and 0.6 nM, respectively. PF-06463922 dose-dependently decreased phosphorylation of SLC34A2-ROS1 and downstream signaling molecules SHP2, Erk1/2, and AKT in HCC78 cells.

Animal experiment [1]:

Animal models

mice bearing FIG-ROS1 glioblastoma multiforme (GBM) tumors

Dosage form

10 mg/kg/d; s.c. osmotic pumps; 3-, 7-, or 14-d treatment

Application

In mice bearing FIG-ROS1 GBM tumors, PF-06463922 significantly regressed the GBM LSL-FIG-ROS1;Cdkn2a-/-;LSL-Luc tumors following a 7-d and 14-d treatment. PF-06463922 reduced overall tumor cell size and the number of Ki67-positive cells. PF-06463922 reduced pFIG-ROS1, pSHP2, pMEK1/2, and pERK1/2 in tumor cell lysates.

Other notes

Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal.

References:

[1]. Zou HY, Li Q, Engstrom LD, et al. PF-06463922 is a potent and selective next-generation ROS1/ALK inhibitor capable of blocking crizotinib-resistant ROS1 mutations. Proceedings of the National Academy of Sciences, 2015, 112(11): 3493-3498.

产品描述

PF-06463922 is a potent and selective ALK/ROS1 inhibitor with IC50 values ranging from 0.19-0.53 nM for the kinase activity of ROS1 fusion enzymes [1].

The receptor tyrosine kinase c-ros oncogene1 (ROS1) is a receptor with a kinase domain that is related to the anaplastic lymphoma kinase/lymphocyte-specific protein tyrosine kinase (ALK/LTK) and insulin receptor (INSR) RTK families [1].

Via cellular ROS1 autophosphorylation in the recombinant enzyme assay, PF-06463922 showed a 30-fold improved potency against ROS1, compared with crizotinib, ceritinib, alectinib and foretinib (XL-880). Engineered NIH 3T3 cells were expressing oncogenic human ROS1 fusions. In these cells, PF-06463922 was more potent than foretinib and crizotinib by >10 folds, more potent than alectinib and ceritinib by >100 folds against cellular ROS1 autophosphorylation [1].

Oncogenic gene fusions involving the 3' region of ROS1 kinase had been found in various human cancers [2]. Mice bearing CD74-ROS1, CD74-ROS1G2032R and FIG-ROS1(S) s.c. Tumors (250 mm3) were used. Treatments with PF-06463992 at various doses were applied consecutively for 7 or 9 d. At dosages of 0.2 to 1 mg/kg/d, PF-06463922 significantly inhibited the growth of both established FIGROS1(S) and CD74-ROS1 tumors compared with vehicle control. At 2-6 mg/kg/d, PF-06463922 significantly made tumor volumes regress (58–85%, P < 0.0001). In animals bearing NIH 3T3-CD74-ROS1G2032R tumors, treatment with PF-06463922 at 1.0, 3.0, and 10 mg/kg/d significantly inhibited tumor growth by 28%, 44% and 90%, respectively. At 30 mg/kg/d, PF-06463922 made tumor regress by 12%, compared with vehicle [1].

References:
[1].  Zou HY, Li Q, Engstrom LD, et al. PF-06463922 is a potent and selective next-generation ROS1/ALK inhibitor capable of blocking crizotinib-resistant ROS1 mutations. Proceedings of the National Academy of Sciences, 2015, 112(11): 3493-3498.
[2].  Davies KD, Le AT, Theodoro MF, et al. Identifying and targeting ROS1 gene fusions in non–small cell lung cancer. Clinical Cancer Research, 2012, 18(17): 4570-4579.

Chemical Properties

Cas No. 1454846-35-5 SDF
别名 劳拉替尼; PF-06463922
Canonical SMILES FC1=CC([C@H](OC2=C(N)N=CC(C3=C(C#N)N(C)N=C3CN4C)=C2)C)=C(C4=O)C=C1
分子式 C21H19FN6O2 分子量 406.41
溶解度 ≥ 20.3mg/mL in DMSO 储存条件 Store at -20°C
General tips 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°C 储存时,请在 6 个月内使用,-20°C 储存时,请在 1 个月内使用。
为了提高溶解度,请将管子加热至37℃,然后在超声波浴中震荡一段时间。
Shipping Condition 评估样品解决方案:配备蓝冰进行发货。所有其他可用尺寸:配备RT,或根据请求配备蓝冰。

溶解性数据

制备储备液
1 mg 5 mg 10 mg
1 mM 2.4606 mL 12.3028 mL 24.6057 mL
5 mM 0.4921 mL 2.4606 mL 4.9211 mL
10 mM 0.2461 mL 1.2303 mL 2.4606 mL
  • 摩尔浓度计算器

  • 稀释计算器

  • 分子量计算器

质量
=
浓度
x
体积
x
分子量
 
 
 
*在配置溶液时,请务必参考产品标签上、MSDS / COA(可在Glpbio的产品页面获得)批次特异的分子量使用本工具。

计算

动物体内配方计算器 (澄清溶液)

第一步:请输入基本实验信息(考虑到实验过程中的损耗,建议多配一只动物的药量)
给药剂量 mg/kg 动物平均体重 g 每只动物给药体积 ul 动物数量
第二步:请输入动物体内配方组成(配方适用于不溶于水的药物;不同批次药物配方比例不同,请联系GLPBIO为您提供正确的澄清溶液配方)
% DMSO % % Tween 80 % saline
计算重置