Elesclomol 是一种氧化应激诱导剂，可诱导癌细胞凋亡。它还是一种高度亲脂性的 Cu2+结合分子，可用于 Menkes 和遗传性铜缺乏症相关疾病的研究。

Elesclomol (STA-4783) is an effective oxidative stress inducer that elicits pro-apoptosis of tumor cells.

在携带人乳腺癌(MDA435, MCF7和ZR-75-1),肺癌 (RER)或淋巴癌 (U937)的裸鼠模型中,尽管 Elesclomol（25-100 mg/kg）单独处理没有抗癌活性,但其可大幅增强化如紫杉醇等疗药物的功效,可使肿瘤衰退,也可延长小鼠寿命.

Elesclomol对SK-MEL-5、MCF-7,和HL-60细胞的活力有明显抑制（IC50：110/24/9 nM）。Elesclomol可诱导酵母细胞铜依赖性的ROS生成和毒性,与作用于细胞内特定靶点不同,Elesclomol与电子传递链相互作用, 电子传递链在细胞器中获得高水平的ROS,从而使细胞死亡。使用Affymetrix 基因芯片分析, Elesclomol（100 nM）处理Hs294T细胞6小时,明显诱导热休克应激反应基因和金属硫蛋白基因的表达。 Elesclomol（100 nM）处理Ramos Burkitt‘s淋巴瘤 B细胞1小时和6小时,可诱导Hsp70 RNA水平快速提高4.8倍和160倍,Elesclomol处理 0.5小时和6小时,ROS含量分别提高20%和385%,抗氧化剂N-乙酰半胱氨酸和Tiron预处理可抑制对Hsp70的诱导作用。Elesclomol（200 nM）处理HSB2细胞18小时,通过诱导氧化应激,提高早期和晚期凋亡细胞分别为3.7和11倍。

In vitro enzyme assays for PLK1: Recombinant PLK1 (10 ng) is incubated with different concentrations of Rigosertib in a 15 μL reaction mixture (50 mM HEPES, 10 mM MgCl2, 1 mM EDTA, 2 mM Dithiothreitol, 0.01% NP-40 [pH 7.5]) for 30 min at room temperature. Kinase reactions are performed for 20 min at 30 °C in a volume of 20 μL (15 μL enzyme + inhibitor, 2 μL 1 mM ATP), 2 μL of γ32P-ATP (40 μCi), and 1 μL of recombinant Cdc25C (100 ng) or casein (1 μg) substrates. Reactions are terminated by boiling for 2 min in 20 μL of 2× Laemmli buffer. Phosphorylated substrates are separated by 18% SDS-PAGE. The gels are dried and exposed to X-ray film for 3-10 min.

Cells are treated with various concentrations of Elesclomol for 18 or 24 hours. The level of intracellular ROS is monitored using the DCFDA probe, which emits a green fluorescence on oxidation. Cell death is determined by flow cytometry of cells double stained with Annexin V/FITC and propidium iodide (PI) using a Vybrant Apoptosis assay kit.(Only for Reference)

488832-69-5

C19H20N4O2S2

400.5

伊利司莫;STA-4783

DMSO:74 mg/mL (184.8 mM)
Ethanol:<1 mgml
Powder: -20°C for 3 years
In solvent: -80°C for 2 years