Olivier Mailhot and his team develop computational tools to accelerate the discovery of small molecules that modulate therapeutic targets, with a focus on cancer. Their research combines structure-based drug design, artificial intelligence, and close collaboration with experimental teams to identify new drug candidates more efficiently.

Research theme

The Mailhot Lab focuses on virtual screening, a cornerstone of early drug discovery. Advances in chemical synthesis have enabled the creation of massive “make-on-demand” libraries, comprising hundreds of billions of small molecules that can be synthesized within weeks. These virtual compounds, many of which have never existed before, hold enormous therapeutic potential, but navigating this immense space requires powerful computational tools.

To address this challenge, the Mailhot Lab develops prioritization algorithms that accelerate molecular docking, allowing the team to screen up to 10 trillion molecules against a given protein target. These techniques are used to identify novel ligands for disease-relevant proteins, with a focus on cancer targets studied at IRIC. The team combines structural modeling, literature-based curation, and control experiments to ensure accuracy and relevance throughout the virtual screening process.

Research objectives

The lab aims to transform the front end of drug discovery by designing and applying advanced computational approaches that can identify high-quality hits from ultra-large libraries of synthesizable compounds. A key priority is the development of scalable prioritization algorithms that improve the speed and accuracy of molecular docking, enabling the efficient identification of compounds with strong binding affinity and novel chemical structure.

Beyond hit discovery, the lab integrates predictive models of pharmacokinetics and toxicity (PK/Tox) into the screening process. This helps filter out compounds with poor drug-like properties early on, guiding the selection of safer and more effective candidates. In close collaboration with IRIC’s medicinal chemistry and biology teams, top-ranked compounds are synthesized and tested in vitro and in vivo to validate activity and refine their pharmacological profiles. Through this integrated pipeline, the Mailhot Lab contributes both chemical tools to probe biological mechanisms and therapeutic leads with potential for clinical translation.