Oltipraz (RP 35972) is a synthetic dithiolethione with potential chemopreventive and anti-angiogenic properties. Oltipraz induces phase II detoxification enzymes, such as glutathione S transferase (GST) and NAD(P)H: quinone oxidoreductase 1 (NQO1). The induction of detoxification enzymes enhances the detoxification of certain cancer-causing agents, thereby enhancing their elimination and preventing carcinogen-induced DNA damages. Although the exact mechanism through which the anti-angiogenesis effect remains to be fully elucidated, oltipraz maybe able to modulate the expression of a number of angiogenic factors, thereby blocking the sustained and focal neovascularization in multiple tumor cell types.

HIF1α:10 μM

作为一种化学保护剂，Oltipraz 能以 Nrf2 依赖性方式诱导第二阶段解毒酶的活性。[1] 在人类 HT29 结肠癌细胞中，奥替普拉唑通过显著加速 HIF-1α 蛋白的降解，抑制胰岛素、缺氧或 CoCl2 对 HIF-1α 的诱导。[2]

Oltipraz（500 mg/kg，口服）可显著降低野生型小鼠胃肿瘤的复发率 55%，但对 nrf2 缺失型小鼠的肿瘤负荷没有影响。[1] 在移植了 HCT116 细胞的 BALB/c 裸鼠体内，Oltipraz（200 mg/kg，口服）通过抑制 HIF-1α 抑制肿瘤生长和血管生成。[2] 在以 CDAA 为食的大鼠中，Oltipraz 可减轻非酒精性脂肪性肝炎相关纤维化的进展。[3]

The Src and Abl kinase assays: The Src kinase activity is measured in an ELISA format. Src (3 units/reaction), reaction buffer (50 mM Tris-HCl pH 7.5, 10 mM MgCl2, 0.1 mM EGTA, 0.5 mM Na3VO4) and cdc2 substrate peptide are added to various concentration of Bosutinib and incubated at 30 °C for 10 minutes. The reaction is started by the addition of ATP to a final concentration of 100 μM, incubated at 30 °C for 1 hour and stopped by addition of EDTA. Instructions from the manufacturer are followed for subsequent steps. The Abl kinase assay is performed in a DELFIA solid phase europium-based detection assay format. Biotinylated peptide (2 μM) is bound to streptavidin-coated microtitration plates for 1.5 hours in 1 mg/mL ovalbumin in PBS. The plates are washed for 1 hour with PBS/0.1% Tween 80, followed by a PBS wash. The kinase reaction is incubated for 1 hour at 30°C. Abl kinase (10 units) is mixed with 50 mM Tris-HCl (pH 7.5), 10 mM MgCl2, 80 μM EGTA, 100 μM ATP, 0.5 mM Na3VO4, 1% DMSO, 1 mM HEPES (pH 7.0), 200 μg/mL ovalbumin and various concentration of Bosutinib. The reaction is stopped with EDTA at a final concentration of 50 mM. The reaction is monitored with Eu-labeled phosphotyrosine antibody and DELFIA enhancement solution.