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OALib Journal期刊
ISSN: 2333-9721
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蛋白酪氨酸磷酸酶shp2抑制剂体外筛选模型的建立及应用
DOI: 10.3724/SP.J.1145.2015.01040, PP. 602-606
Keywords: shp2,抑制剂,体外筛选,shandougeninea
Abstract:
蛋白酪氨酸磷酸酶shp2（srchomologyphosphotyrosylphosphatase2）参与了jak/stat、nf-κb和p13k/akt等诸多信号途径的调控，与努南综合征、单核细胞白血病、骨髓增生异常综合征、b细胞急性淋巴细胞白血病和急性髓性白血病等疾病密切相关.因此，建立稳定可靠的体外shp2抑制剂筛选模型，对于发现高效的化学小分子探针并深入研究相关机制，以及开发新药物治疗相关疾病具有重要意义.通过应用大肠杆菌系统克隆表达可溶的gst-shp2融合蛋白，以矾酸钠（na3vo4）为阳性抑制剂，本文建立基于96孔板的shp2体外筛选模型，并对该模型的有效性进行评价.利用该筛选模型筛选了1431个化合物，发现从植物山豆根（sophoratonkinensis）中提取得到的化合物shandougeninea对shp2具有明显的抑制作用，进一步研究发现其浓度依赖性抑制shp2活性，ic50值为(11.72±2.6)μmol/l.本文筛选模型的建立，为发现shp2抑制剂提供了一条简便高效的途径，并为后续的机制研究及药物开发奠定了良好基础.
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