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. Most drug discovery efforts by pharmaceutical companies concern the development and/or expansion of their pre-clinical and clinical pipeline primarily targeting G protein-coupled receptors, nuclear receptors, ion channels and the active sites of enzymes (eg kinases). Although this strategy is understandable for historical reasons and risk management, inhibitors of protein-protein interaction represents an alternative and almost unexplored reservoir for drug development in oncology. Thus, targeting protein-protein interaction interfaces appears a valuable and promising strategy, which is further underscored by an expected reduced occurrence of resistance that might arise due to mutations in the protein-protein interface. 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.
Yves Collette and Xavier Morelli
Yves Collette (INSERM) - Xavier Morelli (CNRS)
Laboratory of integrative Structural & Chemical Biology (iSCB)
Cancer Research Center of Marseille (CRCM)
INSERM U 1068 / CNRS UMR 7258
Université Aix-Marseille / Institut Paoli Calmettes
27 Boulevard Leï Roure-BP30059
13273 Marseille Cedex 09
TrGET is a preclinical platform, performing and developping in vitro and in vivo testing of target genes involved in tumorogenesis or antitumoral therapeutics. Great efforts are provided towards technological developments, including assay, tool and both cell and animal proposed models. TrGET affers a variety of flexible and customizable services, with privileged development of bioluminescence-based technologies (in vitro or in vivo).
- Staff: Y. Collette (20%), R. Castellano, A. Restouin (50%), L. Pouyet (50%), A. Goubard.
The INT-3D platform has been created at the beginning of 2008 by Dr. Xavier Morelli and Dr. Philippe Roche to answer to an increasing demand of the academic laboratories regarding molecular modeling (virtual mutagenesis mainly) and virtual screening (hit finding and hit to lead optimization).
- Staff: X. Morelli (20%) - P. Roche (20%) - MJ. Basse (50%)