4-[3-(2-Chlorophenyl)-2-propen-1-ylidene]-1-phenyl-3,5-pyraz

中文名称:

4-[3-(2-Chlorophenyl)-2-propen-1-ylidene]-1-phenyl-3,5-pyrazolidinedione

中文同义词:

英文名称:

4-[3-(2-Chlorophenyl)-2-propen-1-ylidene]-1-phenyl-3,5-pyrazolidinedione

英文同义词:

4-[3-(2-Chlorophenyl)-2-propen-1-ylidene]-1-phenyl-3,5-pyrazolidinedione;CPYPP;3,5-Pyrazolidinedione, 4-[3-(2-chlorophenyl)-2-propen-1-ylidene]-1-phenyl-

CAS号:

310460-39-0

分子式:

C18H13ClN2O2

分子量:

324.76

EINECS号:

相关类别:

API

Mol文件:

310460-39-0.mol

密度 

1.405±0.06 g/cm3(Predicted)

储存条件 

Sealed in dry,2-8°C

酸度系数(pKa)

8.26±0.20(Predicted)

生物活性

CPYPP 是一种 DOCK2-Rac1 相互作用的抑制剂。CPYPP 结合 DOCK2DHR-2 结构域，并以剂量依赖性方式抑制 DOCK2DHR-2 对 Rac1 的鸟嘌呤核苷酸交换因子活性，IC50 为 22.8 µM。CPYPP 还抑制 DOCK180 和 DOCK5，对 DOCK9 的抑制活性较少。

靶点

IC50: 22.8 µM (GEF activity of DOCK2 DHR-2 for Rac1)

体外研究

CPYPP binds to DOCK2 DHR-2 domain in a reversible manner and inhibited its catalytic activity in vitro. When lymphocytes are treated with CPYPP, both chemokine receptor- and antigen receptor-mediated Rac activation are blocked, resulting in marked reduction of chemotactic response and T cell activation. Although overexpression of DOCK2 induces Rac activation in HEK293T cells, this activation is markedly suppressed by treating the cells with CPYPP at 100 µM for 1 hr before assay.

体内研究

When 2.5 mg/kg of CPYPP is administrated intravenously, the plasma concentration of CPYPP is only 2.4 µM at 30 min. However, by intraperitoneally injecting 250 mg/kg of CPYPP into mice, the plasma concentration of CPYPP reached to 11.3 µM at 30 min and 10.9 µM at 1 hr, respectively. The adoptively transferred spleen cells from mice that has been made by a ‘‘knock-in’’ strategy to express endogenous DOCK2 as a fusion protein with green fluorescent protein (GFP). Intraperitoneal injection of CPYPP (5 mg per mouse) 1 hr before adoptive transfer reduces the percentage of the migrated T cells to <25% of the control level.