Tie2 kinase inhibitor (Synonyms: Tunica Interna Endothelial Cell Kinase 2 Inhibitor) |
| رقم الكتالوجGC14898 |
مثبط Tie2 kinase (المركب 5) هو مثبط فعال انتقائي Tie2 kinase مع IC50 من 250 نانومتر. مثبط Tie2 kinase له نشاط مضاد للسرطان.
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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]: | |
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Cell lines |
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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. |
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Reaction Conditions |
5µM |
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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]: | |
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Animal models |
NMO rats |
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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. |
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Dosage form |
Intraperitoneal injection, 25 mg/kg for 2 weeks |
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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. |
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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 | |
| المرادفات | Tunica Interna Endothelial Cell Kinase 2 Inhibitor | ||
| Chemical Name | (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 | ||
| Formula | C26H21N3O2S | M.Wt | 439.53 |
| الذوبان | ≥ 22mg/mL in DMSO | Storage | Store at -20°C |
| General tips | Please select the appropriate solvent to prepare the stock solution according to the
solubility of the product in different solvents; once the solution is prepared, please store it in
separate packages to avoid product failure caused by repeated freezing and thawing.Storage method
and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored
at -20°C, please use it within 1 month. To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time. |
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| Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. | ||
| Prepare stock solution | |||
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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 |
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- Purity: >99.00%
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