TARGETED CHEMICAL HIGH-THROUGHPUT SCREENING METHOD

摘要

A novel method which integrates a "sensitized" chemical genetic high-throughput screen (HTS) with RNA interference (RNAi) screening technology is described herein. The present inventors used this method to identify specific small molecule inhibitors and activators of the Wnt pathway. More particularly, the screening method of the present invention may be used to identify small molecule inhibitors and activators that specifically target the activity of a stabilized pool of ß-catenin. A number of compounds identified using the instant method, are shown herein to be small molecule inhibitors of the Wnt pathway that specifically target the activity of the stabilized pool of ß-cat. The inhibitors identified by the present method may be prepared as pharmaceutical compositions, and may be used for the prevention and treatment of a variety of conditions in mammals including humans, including by way of non-limiting example, cancer, and others.