487020-03-1

中文名称:

487020-03-1

中文同义词:

TOPK抑制剂(HI-TOPK-032)

英文名称:

N-(12-Cyanindolizino[2,3-b]quinoxalin-2-yl)-2-thiophenecarboxaMide

英文同义词:

N-(12-Cyanindolizino[2,3-b]quinoxalin-2-yl)-2-thiophenecarboxaMide;HI-TOPK-032;HI-TOPK-32;N-(12-Cyanoindolizino[2,3-b]quinoxalin-2-yl)-2-thiophenecarboxamide;HI-TOPK-032 (HI TOPK 032;2-Thiophenecarboxamide, N-(12-cyanoindolizino[2,3-b]quinoxalin-2-yl)-

CAS号:

487020-03-1

分子式:

C20H11N5OS

分子量:

369.4

EINECS号:

相关类别:

细胞生物学试剂;Aromatics, Heterocycles, Pharmaceuticals, Intermediates Fine Chemicals, Sulfur Selenium Compounds

Mol文件:

487020-03-1.mol

沸点 

415.3±45.0 °C(Predicted)

密度 

1.50±0.1 g/cm3(Predicted)

储存条件 

2-8°C

溶解度 

DMSO: soluble3mg/mL, clear (warmed)

形态

powder

酸度系数(pKa)

9.32±0.46(Predicted)

颜色

orange-brown

生物活性

HI-TOPK-032 是一种有效的、特异性的 TOPK 的抑制剂。HI-TOPK-032 还可以降低 ERK-RSK 磷酸化，调节 p53、裂化的 caspase-7 和裂化的 PARP 的丰度，并在癌细胞中诱导凋亡。

靶点

Target Value TOPK () ERK-RSK () p53 () Caspase-7 () PARP ()

Target

Value

TOPK ()

ERK-RSK ()

p53 ()

Caspase-7 ()

PARP ()

体外研究

HI-TOPK-032 strongly suppresses TOPK kinase activity but 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. However, HI-TOPK-032 at the highest concentration (5 μM) also inhibits MEK1 activity by 40%. HI-TOPK-032 also 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.

体内研究

Treatment of mice with 1 or 10 mg/kg of HI-TOPK-032 significantly 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 induced, and phosphorylation of ERK and RSK, a direct downstream protein of ERK, is markedly inhibited in the HI-TOPK-032-treated group.

危险品标志 

Xn

危险类别码 

22

WGK Germany 

3