Kinases are critical proteins playing a role in the cascade transmission of cell signals transferring phosphate groups from ATP or ATP-like molecules to substrates (phosphorylation process). They are directly involved in numerous diseases, particularly cancer and inflammation, and became one of the most studied family of receptors for the development of new drugs. More than 500 kinases were identified in humans and could be suitable targets.

Commercialisation of imatinib (Gleevec) for the treatment of chronical leukemia, of gefitinib (Iressa) and erlotinib (Tarceva) for the treatment of lung cancer showed that small molecules inhibiting protein kinases could be efficient drugs. More than 40 kinase inhibitors are currently analysed in pre-clinical studies. Most of those molecules target the ATP site of the kinase but researchers also try to inhibit the non-ATP site to obtain selectivity.

For a better understanding of the mechanisms of those proteins, new approaches and structures are needed to identify ligands. Kinases were clustered with respect to the homology of their structure. The existence of privileged scaffolds was demonstrated for some families. Parallel synthesis allows to rapidly assess the potential of new chemical series. Molecular models are also useful when trying to select the appropriate combinations (eg : Gozalbes, R. ; Simon, L. ; Froloff, N. ; Sartori, E. ; Monteils, C. ; Baudelle, R. “Development and Experimental Validation of a Docking Strategy for the Generation of Kinase-Targeted Librairies” J. Med. Chem., 2008, 51, 3124-3132.)