The central activity of the CMBC unit is to develop small molecules to probe and control the biological activities of key targets involved in cancer. These are non B-nucleic acid structures (G-quadruplexes, Abasic sites, …) and proteins (TAM kinases, non B-nucleic acid structures interacting proteins, …).
The drug and probe discovery activity is sustained by molecular modelling approaches and imaging. The CMBC unit is hosting the Institut Curie–CNRS proprietary library comprised of over 9000 chemical compounds.
The main research themes of the unit include:
- Design and synthesis of G-quadruplex targeting agents for probing, imaging and mapping
- Design, synthesis and studies of novel small-molecule ligands and probes able to recognize unusual DNA and RNA structures
- Screening approaches and rational design for the synthesis of kinase inhibitors
- Identificaction of radiosensitizing molecules for the treatment of cancers and determination of their molecular mechanisms of action
The main methodological approaches are :
- Chemical biology
- Medicinal chemistry (Hit to lead optimization)
- Biophysics and Biochemistry of nucleic acids
- Molecular dynamics and virtual screening
- Cellular biology & radiosensitization
Key publications
Year of publication 2021
Jérémie Mitteaux, Pauline Lejault, Filip Wojciechowski, Alexandra Joubert, Julien Boudon, Nicolas Desbois, Claude P. Gros, Robert H. E. Hudson, Jean-Baptiste Boulé, Anton Granzhan, David Monchaud (2021 Aug 4)
Identifying G-Quadruplex-DNA-Disrupting Small Molecules
Journal of the American Chemical Society : 143 : 12567–12577 : DOI : 10.1021/jacs.1c04426
Marc Lavigne, Olivier Helynck, Pascal Rigolet, Rofia Boudria-Souilah, Mireille Nowakowski, Bruno Baron, Sébastien Brülé, Sylviane Hoos, Bertrand Raynal, Lionel Guittat, Claire Beauvineau, Stéphane Petres, Anton Granzhan, Jean Guillon, Geneviève Pratviel, Marie-Paule Teulade-Fichou, Patrick England, Jean-Louis Mergny, Hélène Munier-Lehmann (2021 Jul 7)
SARS-CoV-2 Nsp3 unique domain SUD interacts with guanine quadruplexes and G4-ligands inhibit this interaction.
Nucleic Acids Research : 49 : 7695–7712 : DOI : 10.1093/nar/gkab571
Piguel S., Le Bescont J., Mouawad L., Boddaert T., Bombard S. (2021 Jun 29)
Photoactivatable small-molecule inhibitors for light-controlled TAM kinase activity
ChemPhotoChem : Accepted Author Manuscript : DOI : 10.1002/cptc.202100131
Samar Ali, Emilia Puig Lombardi, Deepanjan Ghosh, Tao Jia, Géraldine Vitry, Lina Saker, Joël Poupon, Marie-Paule Teulade-Fichou, Alain Nicolas, Arturo Londono-Vallejo, Sophie Bombard (2021 May 22)
Pt-ttpy, a G-quadruplex binding platinum complex, induces telomere dysfunction and G-rich regions DNA damage.
Metallomics : integrated biometal science : 13 : mfab029 : DOI : 10.1093/mtomcs/mfab029
Laura Fourmois, Florent Poyer, Aude Sourdon, Delphine Naud-Martin, Sounderya Nagarajan, Rahima Chennoufi, Eric Deprez, Marie-Paule Teulade-Fichou, Florence Mahuteau-Betzer (2021 May 19)
Modulation of cellular fate of vinyl triarylamines through structural fine tuning: to stay or not to stay in the mitochondria?
Chembiochem : a European journal of chemical biology : Accepted Article : DOI : 10.1002/cbic.202100168
Abegão L.M., Santos F.A., Piguel S., Rodrigues J.J., Mendonça C.R., De Boni L. (2021 Apr 15)
