Olivier Mailhot and his team develop computational tools for discovering small molecules that modulate therapeutic targets involved in cancer. Their research combines structure-based drug discovery, artificial intelligence, and close collaboration with experimental teams to more effectively identify new drug candidates.

Research theme

The Mailhot laboratory uses virtual screening by molecular docking, a key step at the beginning of the drug discovery process. Advances in chemical synthesis have enabled the creation of vast libraries of “made-to-order” molecules, currently numbering in the trillions, which can be synthesized in a matter of weeks. These virtual compounds, most of which have never been synthesized before, have strong therapeutic potential, but exploring them requires cutting-edge computational tools.

To meet this challenge, the laboratory is developing prioritization algorithms that accelerate docking, making it possible to evaluate entire virtual libraries (currently 10¹³ molecules) against a given target. These approaches are used to identify new ligands capable of modulating proteins involved in various diseases, particularly cancer-related targets studied at IRIC. The team combines structural modeling, analysis of literature data, and control experiments to ensure the relevance and reliability of the screening process.

Research objectives

The laboratory aims to transform the early stages of drug discovery by developing advanced computational approaches capable of identifying promising compounds within very large libraries. A major priority is the development of effective prioritization algorithms that accelerate screening while maintaining high accuracy, in order to discover molecules with high binding affinity and novel chemical structures.

Beyond the identification of active compounds, the laboratory integrates predictive models of pharmacokinetics and toxicity (ADMET) into the selection process. This makes it possible to eliminate molecules with an unfavorable pharmacological profile upstream and to guide the selection of safer and more effective candidates. Working closely with IRIC’s medicinal chemistry and biology teams, the best compounds are synthesized and tested in vitro and in vivo to validate their activity and refine their pharmacological profile. Thanks to this integrated pipeline, the laboratory contributes both to the creation of molecular tools for elucidating the biology of targets and to the development of new therapeutic avenues.