OTS514 hydrochloride is a highly effective TOPK(T-LAK cell-originated protein kinase) inhibitor (IC50: 2.6 nM).

TOPK:2.6 nM

OTS514能够抑制表达TOPK较高的肾癌细胞系(VMRC-RCW, Caki-1, Caki-2, 769-P, 和 786-O)的生长(IC50:19.9-44.1 nM)[1]。此外，OTS514对TOPK阳性癌细胞的生长抑制作用显著，亦对卵巢癌细胞系显现出显著的生长抑制效果(IC50: 3.0-46 nM)[3]。

在使用人类肺癌细胞进行的小鼠异种移植研究中，OTS514展现了一定的疗效，但也引发了严重的血液毒性（红细胞和白细胞减少，伴随明显的血小板增加）[2]。与对照组（P < 0.001）相比，OTS514（口服）显著延长了ES-2腹膜转移异种移植模型中的总生存时间。

Cell lines: CD34+ HSCs. Concentrations: 20 or 40 nM. Incubation Time: 48 h. Method: Cells were cultured in RPMI supplemented with 20% fetal bovine serum and 1×StemSpan CC100.Cells were treated with OTS514 (20 or 40 nM) or OTS964 (100 or 200 nM) for 48 hours.Collected cells were washed with PBS and resuspended in 100 ml of PBS followed by staining with CD41a antibody for 20 min at room temperature.Finally,the cells were washed with PBS again and then analyzed for CD41a staining by flow cytometry.Expression of STAT5 was examined by Western blot with an anti-STAT5 antibody.

Animal: BALB/cSLC-nu/nu mice. Solvent: 5% glucose (i.v.); 0.5% methylcellulose (p.o.). Dosages: 1,2.5,and 5 mg/kg