Drug discovery is an inherently inefficient process, particularly in oncology. The difficulty in matching the immense and complex chemical world with a desired physiological effect is illustrated by limitations such as harmful side effects and drug resistance, which defy the most powerful chemotherapeutics available. Novel therapeutic targets and new ways to identify, to characterize and to develop anti-cancer drugs are needed. Inhibitors of protein-protein interaction represents an alternative and almost unexplored reservoir for drug development in oncology. In this context, our objectives are to identify, to understand, to validate and to target protein-protein interaction interfaces critically involved in tumor cell signaling, with the specific purpose of facilitating the transfer of therapeutic and pharmacological targets into preclinical and clinical development programs in oncology.

We have recently implemented an integrated drug discovery approach with an automated process combining chemoinformatics (development of a software dedicated to in silico chemical reaction and systematic energetic –docking- evaluation of the resulting chemical libraries), chemical synthesis (diversity oriented synthesis and hit explosion / Chemspeed SLTII platform) and HTS assays (pharmacological and biophysical evaluation / ECHO platform). This integrative effort will be exemplified with examples of hit(s) discovery and hit-to-lead optimization on Bromodomain or PDZ domain inhibitors development as well as a drug repurposing success of tyrosine kinase inhibitors (imatinib and masitinib).