Our group works on the design of compounds targeting non-B nucleic acid structures and certain kinases involved in cancer. The group has a broad expertise in bio-organic chemistry and optical spectroscopy with a strong background in supramolecular chemistry and molecular recognition. Our final aims are to open new perspectives in the discovery of anticancer drugs and mechanistic tools.
Structure and Fluorescence Probes for G-quadruplex DNA and other non-B secondary structures.
Over the past decade we developed a number of heterocyclic scaffolds and metal complexes able to bind specifically G-quadruplex DNA formed in strategic regions of the genome. The Phen-DC3 compound (Fig1) is one of the best quadruplex-probe used worldwide. We are also interested in targeting local pairing defects such as mismatched DNA using macrocycles (CBIs) of particular 3D topology. Our second line of research concerns the development of IR excitable 2 photon fluorescent probes for optical tracking of nucleic acids and proteins in cells.
Protein kinase Inhibitors
Based on our long-term expertise in purine chemistry we have now in hands several chemical series likely to serve for protein kinase inhibitor discovery. The receptor tyrosine kinase Tyro3 is known to be involved in bladder cancer and to be over-expressed in other cancerous pathologies and therefore is considered a new therapeutic target. In collaboration with biologist and modeller partners at the Institut Curie and with crystallographers, we launched a multidisciplinary program for developing selective inhibitors of Tyro3 (Fig2).
Photosensitizers for Retinoblastoma
The current treatment for retinoblastoma, the most frequent eye tumour in children, exposes the patient to the long-term consequences of chemotherapy. We are exploring an alternative non-mutagenic treatment using glycoconjugated photosensitizers targeting overexpressed lectins specific of this tumour (Fig. 3)
The Institut Curie-CNRS Chemical library
This library is composed of 9000 compounds. Screenings of this collection have led to the identification of a number of inhibitors (LIM-kinase and phosphatase, HIV splicing proteins), now validated in preclinical trials. This has contributed to the creation of three start-up companies. (Abivax, Ecrin Therapeutics, Cellipse).