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, Financial support

  • 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.
  • Weylchem Innotec, Frankfurt, Germany
 

People

Permanent members

Non-permanent members

  • Mathilde Defois (PhD)
  • Théo Frazier (PhD)
  • Killian Malosse (M2 Sciences du Médicament)

 

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
  • N. Mast, W. Erb, L. Nauton, P. Moreau, O. Mongin, T. Roisnel, M. Macaigne, T. Robert, S. Bach, L. Picot, V. Thiéry, J.-P. Hurvois, F. Mongin. From benzofuro-, benzothieno- and 10-methylindolo-[2,3-b]-fused benzothiopyrano[4,3,2-de]quinolines to the corresponding benzothiopyrano[4,3,2-de]1,8-naphthyridines: synthesis and properties of these hexacyclic heteroaromatic compounds. New J. Chem. 2023, 47, 258-283, doi: 10.1039/D2NJ04567B
  • T. D. Larionova, S. Bastola, T. E. Aksinina, K. S. Anufrieva, J. Wang, V. O. Shender, D. E. Andreev, T. F. Kovalenko, G. P. Arapidi, P. V. Shnaider, A. N. Kazakova, Y. A. Latyshev, V. V. Tatarskiy, A. A. Shtil, P. Moreau, F. Giraud, C. Li, Y. Wang, M. P. Rubtsova, O. A. Dontsova, M. Condro, B. M. Ellingson, M. I. Shakhparonov, H. I. Kornblum, I. Nakano, M. S. Pavlyukov. Alternative RNA splicing modulates the composition of ribosomes and determines spatial phenotype of glioblastoma cells. Nat. Cell Biol. 2022, 24, 1541–1557, doi: 10.1038/s41556-022-00994-w
  • M. Defois, C. Remondin, B. Josselin, L. Nauton, V. Théry, F. Anizon, S. Ruchaud, F. Giraud, P. Moreau. Synthesis and kinase inhibitory potencies of pyrazolo[3,4-g]isoquinolines. Molecules 2022, 27, 5578, doi: 10.3390/molecules27175578
  • E. Auvert, R. Aesoy, F. Giraud, L. Herfindal, F. Anizon, P. Moreau. Synthesis of new pyrazolo[4,3-a]phenanthridine Pim-1 inhibitors and evaluation of their cytotoxic activity towards the MOLM-13 acute myeloid leukemia cell line. Bioorg. Med. Chem. Lett. 2022, 73, 128914, doi: 10.1016/j.bmcl.2022.128914
  • W. Zeinyeh, Y. J. Esvan, B. Josselin, M. Defois, B. Baratte, S. Knapp, A. Chaikuad, F. Anizon, F. Giraud, S. Ruchaud, P. Moreau. Synthesis and biological evaluation of Haspin inhibitors: Kinase inhibitory potency and cellular activity. Eur. J. Med. Chem. 2022, 236, 114369, doi: 10.1016/j.ejmech.2022.114369
  • A. Visseq, A. Descheemaeker, K. Herault, F. Giraud, I. Abrunhosa-Thomas, A. Artola, F. Anizon, R. Dallel, P. Moreau. Improved potency of pyridin-2(1H)one derivatives for the treatment of mechanical allodynia. Eur. J. Med. Chem. 2021, 225, 113748, doi: 10.1016/j.ejmech.2021.113748
  • 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
  • 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. Eur. J. Med. Chem. 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. Bioorg. Chem. 2020, 94, 103347, doi: 10.1016/j.bioorg.2019.103347
  • F. Giraud, E. Pereira, F. Anizon, P. Moreau. Synthesis and applications of dihydropyrrolocarbazoles. European J. Org. Chem. 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. Mol. Cancer Ther. 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. Eur. J. Med. Chem. 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. Bioorg. Med. Chem. 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

Chapters

  • F. Giraud, F. Anizon, P. Moreau. C3-indazole functionalization: a review. Targets in Heterocyclic Systems - Chemistry and Properties Attanasi O. A., Spinelli D., Eds.; Italian Society of Chemistry: Roma, 2021, 100-112, doi: 10.17374/targets.2022.25.100
  • 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