Enzyme and receptor inhibitors group

Group Leader: Pascale Moreau
 

Research subjects

Our research interests mainly focus on the design, synthesis and biological evaluation of heteroaromatic compounds that inhibit kinases involved in cancer, neurodegenerative diseases or pain. In these projects we develop ATP-competitive inhibitors of kinases (CDK, Pim, Dyrk1A…). The design and synthesis of new compounds are carried on in our lab while biological evaluations are performed in collaboration with biologist teams.
 

Research topics

  • Organic synthesis (design, methodology, structural characterization), compounds of biological interest (antitumor, antiparasitic, neurodegenerative diseases, pain).
  • Heteroaromatics: indoles, indazoles, quinoline , aminopyrimidines…
  • Molecular Modelling.
 

Collaborations

  • University of Bergen, Norway: Study of the potency of the prepared compounds toward Acute Myeloid Leukemia.
  • Blokhin Cancer Center, Moscow, Russian Federation: DNA interactions, antiproliferative activities.
  • Station Biologique de Roscoff (France): Study of the potency/selectivity of the prepared compounds to inhibit different kinases.
  • University of Turku, Finland: Study of the Pim-1 kinase function.
  • Oxford University, Angleterre: Crystallographic studies.
  • Laboratoire Neuro-Dol, UMR INSERM 1107, Université Clermont Auvergne: evaluation of analgesic effect on animal models.
  • Centre International de Recherche en Infectiologie, Lyon : antiviral activity.
 

Contracts

  • Région Auvergne-Rhône-Alpes, Pack Ambition Recherche (2020–2024): Vers de nouveaux antalgiques : synthèse et optimisation de nouveaux inhibiteurs de p38α MAPK.
  • Institut National du Cancer, Plan Cancer PCSI (2019-2022): Synthesis and biological evaluation of specific Haspin inhibitors for the development of new anticancer therapies, coordinator Pascale Moreau.
  • Région Auvergne-Rhône-Alpes, Pack Ambition International (2020–2021): Selective cytotoxic agents for the treatment of acute myeloid leukemia, coordinator Fabrice Anizon.
  • Ligue Contre le Cancer – Comité Auvergne (2019): Design, synthesis and biological evaluation of specific haspin inhibitors for the development of novel anti-cancer therapies, coordinator Pascale Moreau.
  • Programme Nouveau Chercheur, région Auvergne (2014-2016): Design and Synthesis of Dyrk1A inhibitors, coordinator F. Giraud.
  • PEPS de site Clermont-Ferrand (2015/2016): Design, synthesis and biological evaluation of PKCγ inhibitors for the study and treatment of mechanical allodynia, coordinator F. Anizon.
 

People

Permanent members

Non-permanent members

  • Arthur Boulangé (Technician)
  • Mohamed Dansokho (Master 2 Sciences du Médicament)
  • Mathilde Defois (PhD)
  • Théo Frazier (PhD)

 

Recent publications

Patent Application
  • R. Dallel, A. Artola, A. Deschemaeker, F. Anizon, I. Thomas, P. Moreau, A. Visseq, F. Giraud. Novel pyridin-2(1H)one derivatives, their preparation and their use for the treatment of pain. PCT Patent application, WO2021/064186.
Articles and reviews
  • F. Giraud, E. Pereira, F. Anizon, P. Moreau. Recent advances in pain management: relevant protein kinases and their inhibitors. Molecules 2021, 26, 2696, doi: 10.3390/molecules26092696
  • F. Anizon, F. Giraud, E. S. Ivanova, D. N. Kaluzhny, A. A. Shtil, F. Cisnetti, P. Moreau. Synthesis and biological activities of new pyrrolocarbazole-imidazobenzimidazole conjugates. Tetrahedron Lett. 2020, 61, 152096, doi: 10.1016/j.tetlet.2020.152096.
  • F. Anizon, P. Moreau. Bicyclic 6–6 systems: other four heteroatoms 2/2. Reference Module in Chemistry, Molecular Sciences and Chemical Engineering, Elsevier Science, 2020, doi: 10.1016/B978-0-12-409547-2.14956-X.
  • Y.J. Esvan, B. Josselin, B. Baratte, S. Bach, S. Ruchaud, F. Anizon, F. Giraud, P. Moreau. Synthesis and kinase inhibitory potencies of new pyrido[3,4-g]quinazolines substituted at the 8-position. Arkivoc 2020, vii, 105–116, doi: 10.24820/ark.5550190.p011.268.
  • A. Visseq, A. Descheemaeker, N. Pinto-Pardo, L. Nauton, V. Théry, F. Giraud, I. Abrunhosa-Thomas, A. Artola, F. Anizon, R. Dallel, P. Moreau. Pyridin-2(1H)one derivatives: a possible new class of therapeutics for mechanical allodynia. European Journal of Medicinal Chemistry 2020, 187, 111917, doi: 10.1016/j.ejmech.2019.111917
  • F. Anizon, P. Moreau, Synthesis and activities of tricyclic pyrido[3,4-g]quinazolines, pyrazolo[3,4-g]quinoxalines and pyrroloindazole regioisomers. Arkivoc 2020, i, 1–19, doi: 10.24820/ark.5550190.p011.110.
  • N. M. Brikci-Nigassa, L. Nauton, P. Moreau, O. Mongin, R. E. Duval, L. Picot, V. Thiéry, M. Souab, B. Baratte, S. Ruchaud, S. Bach, R. Le Guevel, G. Bentabed-Ababsa, W. Erb, T. Roisnel, V. Dorcet, F. Mongin Functionalization of 9-thioxanthone at the 1-position: From arylamino derivatives to [1]benzo(thio)pyrano[4,3,2-de]benzothieno[2,3-b]quinolines of biological interest. Bioorganic Chemistry 2020, 94, 103347, doi: 10.1016/j.bioorg.2019.103347
  • F. Giraud, E. Pereira, F. Anizon, P. Moreau. Synthesis and applications of dihydropyrrolocarbazoles. European Journal of Organic Chemistry 2019, 5025–5042, doi: 10.1002/ejoc.201900269.
  • R. Bjørnstad, R. Aesoy, Ø. Bruserud, A. K. Brenner, F. Giraud, T. H. Dowling, G. Gausdal, P. Moreau, S. O. Døskeland, F. Anizon, Lars Herfindal. A kinase inhibitor with anti-Pim kinase activity is a potent and selective cytotoxic agent towards acute myeloid leukemia. Molecular Cancer Therapeutics 2019, 18, 567–578, doi: 10.1158/1535-7163.MCT-17-1234.
  • H. Tazarki, W. Zeinyeh, Y. J Esvan, S. Knapp, D. Chatterjee, M. Schröder, A. C. Joerger, J. Khiari, B. Josselin, B. Baratte, S. Bach, S. Ruchaud, F. Anizon, F. Giraud, P. Moreau. New pyrido[3,4-g]quinazoline derivatives as CLK1 and DYRK1A inhibitors: synthesis, biological evaluation and binding mode analysis. European Journal of Medicinal Chemistry 2019, 166, 304–317, doi: 10.1016/j.ejmech.2019.01.052.
  • W. Zeinyeh, Y. J. Esvan, B. Josselin, B. Baratte, S. Bach, L. Nauton, V. Théry, S. Ruchaud, F. Anizon, F. Giraud, P. Moreau. Kinase inhibitions in pyrido[4,3-h] and [3,4-g]quinazolines: Synthesis, SAR and molecular modeling studies. Bioorganic and Medicinal Chemistry 2019, 27, 2083–2089, doi: 10.1016/j.bmc.2019.04.005.
  • A. Visseq, T. Boibessot, L. Nauton, V. Théry, F. Anizon, I. Abrunhosa-Thomas. Diastereoselective synthesis of 2,6-disubstituted-1,2,3,6-tetrahydropyridines through a palladium-catalyzed intramolecular allylic amination. Eur. J. Org. Chem. 2019, 7686–7702, doi: 10.1002/ejoc.201901520.
  • B. Douara, Y.J. Esvan, E. Pereira, F. Giraud, Y.L. Volodina, D.N. Kaluzhny, A.A. Shtil, F. Anizon, P. Moreau. Synthesis and antiproliferative evaluation of glucosylated pyrazole analogues of K252c. Tetrahedron 2018, 74, 892-901, doi: 10.1016/j.tet.2018.01.017.