Tie2 kinase inhibitor 1 (Tie2 kinase inhibitor), an optimized compound of SB-203580, is selective to Tie2 with IC50 of 0.25 μM, which is 200-fold more effective than p38.

Tie2:0.25 μM

在HEL细胞中，Tie2激酶抑制剂（IC50=232 nM）展现出中等的细胞活性。Tie2 kinase inhibitor 1对Tie2酪氨酸激酶1具有中等的抑制效果。Tie2 kinase inhibitor 1对Tie2的特异性很高，并且对VEGFR2、VEGFR3和PDGFR1β的特异性>10倍。

在Matrigel小鼠血管生成模型中，Tie2 kinase inhibitor 1能够减少血管生成。当Tie2激酶抑制剂的剂量分别为25 mg/kg和50 mg/kg（i.p.，b.i.d）时，血管生成分别减少了41%和70%。在MOPC-315浆细胞瘤异种移植模型中，Tie2 kinase inhibitor 1的治疗导致肿瘤生长的轻度剂量依赖性延迟。

Enzymatic HDAC activity assays: 40 μL enzyme buffer (15 mM Tris HCl pH 8.1, 0.25 mM EDTA, 250 mM NaCl, 10% v:v glycerol) containing HDAC1, 3, 6 or 8 activity, 29 μL enzyme buffer and 1 μL resminostat at different concentrations are added to a 96-well microtitre plate and the reaction started by the addition of 30μL substrate peptide Ac-NH-GGK(Ac)-AMC (HDAC1, 3 and 6 assays, final concentrations 6 μM for HDAC1, 10 μM for HDAC6 and 25 μM for HDAC3/DAD) or Ac-RHK(Ac)K(Ac)-AMC (HDAC8 assay, final concentration 50 μM). After incubation for 3 hours (HDAC1, HDAC6, HDAC8) or 2 hours (HDAC3) at 30°C, the reaction is terminated by the addition of 25 μL stop solution (50 mM Tris HCl pH 8, 100 mM NaCl, 0.5 mg/mL trypsin and 2 μM trichostatin A [TSA]). After incubation at room temperature for further 40 min, fluorescence is measured using a multilabel counter (extinction 355 nm, emission 460 nm) for quantification of AMC generated by tryptic cleavage of the deacetylated peptide. For the calculation of the IC50, the fluorescence in wells without test compound (1% DMSO, negative control) is set as 100% enzymatic activity and the fluorescence in wells with 2 μM TSA (positive control) is set at 0% enzymatic activity (background fluorescence substracted).

In MOPC-315 plasmacytoma xenograft model, Tie2 kinase inhibitor 1(≤50 mg), which is dissolved in 5% EtOH+5%cremophor+90% water, is injected intraperitoneally.