Screen for Ras inhibitors

KRAS癌基因突变发生在大约30%的癌症中，但这些癌症的治疗选择很少。针对KRAS蛋白或其下游效应物的各种策略在过去并没有特别成功。在这个项目中，我们的目标是采取不同的方法来发现KRAS癌蛋白的抑制剂。我们希望使用高通量化学筛选来鉴定特异性导致KRAS蛋白降解的化合物。重要材料和方法一种基于细胞的检测系统，允许以高通量形式监测小分子对KRAS蛋白水平的影响。我们已经在概念验证实验中证明了该分析的可行性，并针对HTS平台进行了优化。我们进行了试点筛选。

BACKGROUND Mutations in the KRAS oncogene occurs in approximately 30% of cancer yet little therapeutic options exist for the treatment of these cancer. Various strategies to target KRAS protein or it's downstream effectors have not been particularly successful in the past. PURPOSE In this project we aim to take a different approach to discovery inhibitors of the KRAS oncoprotein. We wish to use high-throughput chemical screening to identify compounds that specifically causes the degradation of KRAS proteins. SIGNIFICANT MATERIALS AND METHODS An cell-based assay system that allows one to monitor the effect of small molecules on KRAS protein level in a high-throughput format. FY2011 ACCOMPLISHMENT We have demonstrated the the feasibility of the assay in proof-of-concept experiments and optimized it for HTS platforms. We have conducted a pilot screen.