The X-ray structure of the catalytic domain of the EphA3 tyrosine kinase in complex with a previously reported type II inhibitor was used to design two novel quinoxaline derivatives, inspired by kinase inhibitors that have reached clinical development. These two new compounds were characterized by an array of cell-based assays and gene expression profiling experiments. A global chemical proteomics approach was used to generate the drug-protein interaction profile, which suggested suitable therapeutic indications. Both inhibitors, studied in the context of angiogenesis and in vivo in a relevant lymphoma model, showed high efficacy in the control of tumor size.

中文翻译：

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了解吡咯并[3,2-b]喹喔啉衍生物作为激酶抑制剂的作用机理

EphA3酪氨酸激酶催化结构域与先前报道的II型抑制剂复合的X射线结构被用于设计两种新颖的喹喔啉衍生物，其灵感来自已达到临床开发的激酶抑制剂。这两种新化合物的特征在于一系列基于细胞的测定和基因表达谱实验。全球化学蛋白质组学方法用于生成药物-蛋白质相互作用的概况，这表明合适的治疗适应症。在血管生成的背景下以及在相关的淋巴瘤模型中体内研究的两种抑制剂均显示出在控制肿瘤大小方面的高功效。