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.