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.