| CAS |
No.1224887-10-8 |
| 英文名称 |
GSK2256098 |
| 别名 |
GTPL7939 |
| 分子式 |
C20H23ClN6O2 |
| 分子量 |
414.89 |
| 溶解性 |
Soluble in DMSO |
| 纯度 |
≥98% |
| 外观(性状) |
White to brown Solid |
| 储存条件 |
Powder:2-8℃，2 years;Insolvent(母液):-20℃，6 months;-80℃，1 year |
| 运输条件 |
冷藏运输 |
| MDL |
MFCD30502650 |
| SMILES |
O=C(NOC)C1=CC=CC=C1NC2=CC(NC3=CC(C)=NN3C(C)C)=NC=C2Cl |
| 靶点 |
FAK |
| 通路 |
Angiogenesis; Protein Tyrosine Kinase/RTK |
| 背景说明 |
GSK2256098是一种有效的、选择性的、可逆的、ATP竞争性的FAK kinase抑制剂。 |
| 生物活性 |
GSK2256098 is a selective FAK kinase inhibitor， which inhibits growth and survival of pancreatic ductal adenocarcinoma cells.[1-2] |
| In Vitro |
GSK2256098 is a thousand fold more selective for FAK compared to the nearest FAK family member， Pyk2. GSK2256098 inhibits FAK activity through targeting the phosphorylation site of FAK， tyrosine (Y) 397. GSK2256098 inhibits FAK activity or Y397 phosphorylation in cancer cell lines， OVCAR8 (ovary)， U87MG (brain)， and A549 (lung)， at IC50s of 15， 8.5 and 12 nM， respectively. The responses of 6 PDAC cell lines in regards to FAK Y397 phosphorylation or activity to GSK2256098 treatments (0.1–10 μM) ranged from low (less than 20% inhibition) to high (more than 90% inhibition). The least and most sensitive cell lines (PANC-1 and L3.6P1) are selected for further analysis. GSK2256098 inhibition of FAK Y397 phosphorylation correlated with decreased levels of phosphorylated Akt and ERK in L3.6P1 cells. GSK2256098 decreases cell viability， anchorage-independent growth， and motility in a dose dependent manner[1]. |
| In Vivo |
FAK is well-known to play an important role in angiogenesis， proliferation， and apoptosis， so the tumor samples harvested from the therapy experiments are examined. Evaluating CD31， significantly lower microvessel densities in tumors from mice treated with GSK2256098 and Paclitaxel is observed than in tumors from mice in the vehicle control group (Papoptosis are seen in all models that had been treated with combination GSK2256098 and Paclitaxel[2]. |
| 细胞实验 |
PDAC cells are cultured on the wells of a 96-well plate. Ten microliters of MTS is added to the wells (total value: 100 μL). After the plate is kept in a 37°C incubator for 10-30 min， the absorbance at 450 nm wave length of reacted MTS is determined on a microplate reader. The Sigma plot program is used to calculate IC50 of GSK2256098 on cell viability. PDAC cells are cultured on a 6-well plate. When cell confluence reached about 70% in regular medium， the cells are incubated in the medium containing 0.1-10 μM GSK2256098 for 48 or 72 hr. At the end of treatments， cells are re-seeded and kept for 9 d Then， the cells are stained using Clonogenic Reagent， and the blue colonies are counted[1]. |
| 动物实验 |
Mice[2] Female 8- to 12-week-old athymic nude mice are used. For therapeutic experiments， 4×106 Ishikawa or Hec1A cells are inoculated into the uterine horn. Following tumor cell injection， the mice are randomized (n=10 mice per group) according to the following groups: 1) 100 μL of a vehicle control (oral， daily); 2) 75 mg/kg GSK2256098 in 100 μL of vehicle (oral， daily); 3) 2.5 mg/kg Paclitaxel in 200 μL of PBS (intraperitoneal， weekly); and 4) GSK2256098 and Paclitaxel (doses and frequencies given above). Therapy is initiated 10-14 days after tumor injection. The mice are monitored for adverse effects and sacrificed using cervical dislocation four to six weeks after initiation of treatment. At the completion of each experiment， each mouse’s weight， aggregate tumor weight， location， and number of tumor nodules are recorded for each treatment group. Tumor samples are processed for further analysis via preservation in optimal cutting temperature medium for frozen section analysis as well as fixed in formalin for paraffin-embedded section analysis. |
| 数据来源文献 |
[1]. Zhang J， et al. A small molecule FAK kinase inhibitor， GSK2256098， inhibits growth and survival of pancreatic ductal adenocarcinoma cells. Cell Cycle. 2014;13(19):3143-9.
[2]. Thanapprapasr D， et al. PTEN Expression as a Predictor of Response to Focal Adhesion Kinase Inhibition in Uterine Cancer. Mol Cancer Ther. 2015 Jun;14(6):1466-75. |
| 规格 |
1mg 2mg 5mg 10mg 25mg |
| 单位 |
瓶 |
中文
英语
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