UMR9187 / U1196 – Chemistry and Modelling for the Biology of Cancer (CMBC)

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 2022

Jaime Franco Pinto, Alexandra Fillion, Patricia Duchambon, Sophie Bombard, Anton Granzhan (2021 Oct 9)

Acridine–O6-benzylguanine hybrids: Synthesis, DNA binding, MGMT inhibition and antiproliferative activity

European Journal of Medicinal Chemistry : 227 : 113909 : DOI : 10.1016/j.ejmech.2021.113909

Year of publication 2021

Joanna Zell, Katerina Duskova, Leïla Chouh, Madeleine Bossaert, Nicolas Chéron, Anton Granzhan, Sébastien Britton, David Monchaud (2021 Sep 22)

Dual targeting of higher-order DNA structures by azacryptands induces DNA junction-mediated DNA damage in cancer cells

Nucleic Acids Research : 49 : 10275–10288 : DOI : 10.1093/nar/gkab796
Aleksandr S. Oshchepkov, Oksana Reznichenko, Dan Xu, Boris S. Morozov, Anton Granzhan, Evgeny A. Kataev (2021 Sep 22)

Dye-functionalized Phosphate-binding Macrocycles: From Nucleotide to G-quadruplex Recognition and “turn-on” Fluorescence Sensing

Chemical Communications : 57 : 10632-10635 : DOI : 10.1039/D1CC04096K
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
Laura Fourmois, Florent Poyer, Aude Sourdon, Delphine Naud-Martin, Sounderya Nagarajan, Rahima Chennoufi, Eric Deprez, Marie-Paule Teulade-Fichou, Florence Mahuteau-Betzer (2021 Jul 15)

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 : 22 : 2457-2467 : DOI : 10.1002/cbic.202100168
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