Project information
Novel eIF4F inhibitors for the treatment of drug-resistant melanoma

The eIF4F complex activity is a nexus of melanoma resistance to clinically used MEK and BRAF inhibitors. However, no eIF4F inhibitor is approved for clinical use. Furthermore, the spectrum of small molecule compounds targeting eIF4F is limited, possibly due to the need for techniques suitable for high-throughput screening chemical libraries. We recently developed a unique eIF4F inhibitor screening platform fully compatible with HTS and validated it in a pilot screen of 5,000 bioactive compounds. Subsequent HTS screens of large high-diversity chemical libraries of over 80 thousand compounds yielded many positive hits. This project will enable us to proceed to the hit-to-lead stage of drug development. We will validate in orthogonal assays and characterize in detail the biological activity of over 200 most potent hits, and identify leads suitable for subsequent development into clinical drugs.