Tie2 kinase inhibitor
(Synonyms: Tunica Interna Endothelial Cell Kinase 2 Inhibitor) 目录号 : GC14898
Tie2 kinase inhibitor是一种可逆的选择性Tie2抑制剂，IC50为250 nM。
Cas No.:948557-43-5
Sample solution is provided at 25 µL, 10mM.
Tie2 kinase inhibitor is a reversible and selective inhibitor of Tie2 with an IC50 of 250 nM [1].
Tie2 kinase inhibitor (2 µM) clearly decreased phosphorylation of AKT in TDEC IR- and in TDEC IR+ (TDEC obtained from irradiated GSC). Tie2 kinase inhibitor (2 µM) induced a significant decrease in the number of CD31+ TDEC obtained from non-irradiated SRA5 and SRB1 GSC, but not from non-irradiated SRC3 GSC [2]. Treatment with Tie2 kinase inhibitor (0-3 µg/ml) resulted in significant reduction of both invadopodia and colony formation in fibrin-fibronectin embedded B16F1 cells [3]. SRSF1-WT transfected cells showed more sensitivity to Tie2 kinase inhibition, and SRSF1-Y19F cells showed resistant to the Tie2 kinase inhibitor compared to the empty vector-transfected cells. Tie2 kinase inhibitor showed more intensive effect on the colony-forming properties of SRSF1-WT cells [4]. Tie2 kinase inhibitor(5 µM)treatment decreased P-Akt of primary rat PitNET cells [5].
After subcutaneous implantation of the plugs containing the cells, mice were injected twice daily with the vehicle or the Tie2 kinase inhibitor for 14 days, plugs with TDEC IR+ with Tie2 kinase inhibitor had significantly fewer functional blood vessels than plugs with TDEC IR+ control. The number of hCD31+ vessels was also lower in plugs with TDEC IR+ with Tie2 kinase inhibitor compared to plugs with TDEC IR+ control [2].
References:
[1]. Semones M, Feng Y, Johnson N, et al. Pyridinylimidazole inhibitors of Tie2 kinase[J]. Bioorganic & medicinal chemistry letters, 2007, 17(17): 4756-4760.
[2]. Deshors P, Toulas C, Arnauduc F, et al. Ionizing radiation induces endothelial transdifferentiation of glioblastoma stem-like cells through the Tie2 signaling pathway[J]. Cell death & disease, 2019, 10(11): 1-15.
[3]. Knowles L M, Malik G, Pilch J. Plasma fibronectin promotes tumor cell survival and invasion through regulation of Tie2[J]. Journal of Cancer, 2013, 4(5): 383.
[4]. Xu L, Zhang H, Mei M, et al. Phosphorylation of serine/arginine‐rich splicing factor 1 at tyrosine 19 promotes cell proliferation in pediatric acute lymphoblastic leukemia[J]. Cancer science, 2018, 109(12): 3805-3815.
[5]. Karabid N M, Wiedemann T, Gulde S, et al. Angpt2/Tie2 autostimulatory loop controls tumorigenesis[J]. EMBO molecular medicine, 2022, 14(5): e14364.
| Cell experiment [1]: | |
|
Cell lines |
|
|
Preparation Method |
Cells were routinely tested for mycoplasma and maintained in culture for maximum 5-6 passages. A dose-response experiment was performed to identify the best concentration of AMG386 and Tie2 kinase inhibitor (IC50 = 5µg/ml and 5 µM, respectively) to use for GH3 cells. |
|
Reaction Conditions |
5µM |
|
Applications |
AMG386 and Tie2 kinase inhibitor significantly (> 20%) inhibited proliferation of GH3 cells in vitro. Similar results were obtained in rat primary PitNET (R-PitNET) cells. At the molecular level, Tie2 kinase inhibitor treatment decreased P-Akt of primary rat PitNET cells. |
| Animal experiment [2]: | |
|
Animal models |
NMO rats |
|
Preparation Method |
The NMO rats were randomly divided into four groups: the vehicle-treated group, wherein the rats were intravenously injected with 1 ml of phosphate-buffered saline (PBS) daily for 2 weeks; the C16-treated group, wherein the rats were intravenously injected with 2 mg of C16 peptide daily for 2 weeks; the C16 and Tie2 kinase inhibitor-treated group (Tie2 KI + C16 group), wherein the rats were intravenously injected with 2 mg of C16 peptide daily for 2 weeks and intraperitoneally injected with 25 mg/kg of the Tie2 kinase inhibitor daily for 2 weeks; and the C16 peptide and LY294002-treated group (LY294002 + C16 group), wherein the rats were intravenously injected with 2 mg of C16 peptide daily for 2 weeks and intraperitoneally injected with 100 mg/kg of the class I PI3K inhibitor LY294002 daily for 2 weeks. |
|
Dosage form |
Intraperitoneal injection, 25 mg/kg for 2 weeks |
|
Applications |
The Tie2 KI + C16 group showed lower clinical scores at all-time points, except at 4 weeks post-immunization (P.I.), compared to the vehicle control-treated group and at all-time points, except at 4 and 6 weeks P.I., compared to the C16 peptide + LY294002-treated group. |
|
References: [1]: Karabid N M, Wiedemann T, Gulde S, et al. Angpt2/Tie2 autostimulatory loop controls tumorigenesis[J]. EMBO molecular medicine, 2022, 14(5): e14364. | |
| Cas No. | 948557-43-5 | SDF | |
| 别名 | Tunica Interna Endothelial Cell Kinase 2 Inhibitor | ||
| 化学名 | (S)-4-(4-(6-methoxynaphthalen-2-yl)-2-(4-(methylsulfinyl)phenyl)-1H-imidazol-5-yl)pyridine | ||
| Canonical SMILES | O=[S@@](C)C1=CC=C(C=C1)C2=NC(C3=CC=C4C(C=CC(OC)=C4)=C3)=C(C5=CC=NC=C5)N2 | ||
| 分子式 | C26H21N3O2S | 分子量 | 439.53 |
| 溶解度 | ≥ 22mg/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。 | ||
| 制备储备液 | |||
 |
1 mg | 5 mg | 10 mg |
| 1 mM | 2.2752 mL | 11.3758 mL | 22.7516 mL |
| 5 mM | 0.455 mL | 2.2752 mL | 4.5503 mL |
| 10 mM | 0.2275 mL | 1.1376 mL | 2.2752 mL |
| 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 | 只 |
| 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 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Quality Control & SDS
- View current batch:
- Purity: >99.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet