The research activity of the Laboratory IICiMed EA 1155 in the field of oncology involves design, development and mechanistic study of potential new antitumor agents.

This activity is carried out within the framework of the integration of IICiMed in line "From the sea to anticancer therapy" and the group "Heterocyclic modulators of cell cycle kinases, angiogenesis and apoptosis" of Cancéropôle Grand Ouest.

Kinases inhibitors

A first area of work concerns the development of kinases inhibitors involved in different intracellular signaling pathways that play a key role in the regulation of cell growth and proliferation. This topic constitutes an important focus in oncology.

The investigations of CDK1/5, CK1, CLK1, GSK3, DYRK1A, PI3K/Akt/mTOR, allowed us to prepare a chemical library of more than 350 molecules and to identify a lead, active compound on PI3K (P107), in collaboration with the Cell Biology team of Cancéropôle Grand Ouest.

Apoptosis and p53

The second line of research concerns particularly the design of pro-apoptotic molecules through targeting p53, antitumor protein by inducing apoptosis.

One aspect of this targeting involves the reactivation of p53 in tumor cell lines expressing a mutated protein in 273, and thus become unable to induce apoptosis in cells that have undergone DNA damage. It is therefore to develop compounds with a similar activity as PRIMA-1, capable of restoring the functionality of the binding site of p53 on DNA.

A second aspect of this work is to block the inhibitory action of the Mdm2 protein (regulatory protein) on p53, so as to restore the toxicity of p53 on cells initiated in a tumor process. This consists in the development of compounds preventing the interaction mdm2/p53, in analogy to the Nutline-3, the reference molecule.