- 生物活性
Semaxinib (SU5416) 是有效，选择性的 VEGFR (Flk-1/KDR) 抑制剂，IC50 为 1.23 μM。
- 靶点
Flk-1
1.23 μM (IC
50
)
- 体外研究
Semaxinib (SU5416) inhibits VEGF-driven mitogenesis in a dose-dependent manner with an IC
50
of 0.04±0.02 μM (n=3). In contrast, Semaxinib (SU5416) blocks FGF-dependent mitogenesis of HUVECs with an IC
50
of 50 μM (n=10). An IC
50
of 20.26±5.2 μM, which is about 20-fold less in potency on PDGF-dependent autophosphorylation, is observed when SU5416 is tested in NIH 3T3 cells overexpressing the human PDGF receptor β.
- 体内研究
Daily administration of Semaxinib (SU5416) (i.p., 3 mg/kg/day) inhibits the local growth of C6 tumors in the colon. A comparable level of growth inhibition (62% by day 16; P=0.001) is observed for tumors growing in the colon in comparison with ones growing in the hindflank region (54% by day 18; P=0.001). These results indicate that Semaxinib (SU5416) could inhibit tumor growth at a site other than the subcutaneous implantation site, where the preexisting vasculature may be different. Daily treatment with Semaxinib (SU5416) (25 mg/kg) results in a significantly lower tumor growth rate with tumor masses of up to 8% of that present in control animals by day 22 after implantation. Inhibition of tumor growth is clearly preceded by a marked reduction of the tissue area covered by the newly formed glioma microvasculature in the Semaxinib-treated group, indicating a reduced initial tumor vascularization.
医药
合成路线 1（1. 合成：204005-46-9）
产率：10.4 g
合成条件：With piperidine In methanol at 65℃;
实验步骤：向2-甲酰基-3,5-二甲基吡咯（化合物27,7.17g）和二氢吲哚-2-酮（5.0g）的甲醇（100mL）溶液中加入哌啶（1.0mL）。 将混合物在65℃下搅拌过夜。 冷却至室温后，得到的固体得到所需化合物29（10.4g），为黄色固体。
参考文献：
- [1] Bioorganic and Medicinal Chemistry, 2011, vol. 19, # 10, p. 3086 - 3095
