HI-TOPK-032 是一种特异性 TOPK 有效抑制剂。

HI-TOPK-032 is an effective and specific inhibitor of TOPK.

HI-TOPK-032 inhibits anchorage-dependent and -independent colon cancer cell growth by reducing ERK-RSK phosphorylation as well as increasing colon cancer cell apoptosis through regulation of the abundance of p53, cleaved caspase-7, and cleaved PARP. However, HI-TOPK-032 at the highest concentration (5 μM) also inhibits MEK1 activity by 40%. HI-TOPK-032 strongly inhibits TOPK kinase activity. However, it also has little effect on extracellular signal-regulated kinase 1 (ERK1), c-jun-NH2-kinase 1, or p38 kinase activities. HI-TOPK-032 occupies the ATP-binding site of TOPK and fits the binding site very well. The compound forms hydrogen bonds with GLY83 and ASP151 and has a hydrophobic interaction with LYS30.

HI-TOPK-032 (1 or 10 mg/kg; mice) treatment, obviously inhibits HCT-116 tumor growth by more than 60% relative to the vehicle-treated group. Mice are well tolerated with HI-TOPK-032 treatment. The expression of p53 is strongly caused, and phosphorylation of ERK and RSK, a direct downstream protein of ERK. Which is markedly inhibited in the HI-TOPK-032-treated group.

487020-03-1

C20H11N5OS

369.4

DMSO:7 mg/mL (18.94 mM)
Powder: -20°C for 3 years
In solvent: -80°C for 2 years