Laboratoire de Chimie et Biochimie
Pharmacologiques et Toxicologiques (LCBPT)
CNRS UMR 8601
Université Paris Descartes
45 Rue des Saints Pères
75270 Paris Cedex 06
France

Francine ACHER

Senior Research Scientist, CNRS

Curriculum Vitae

Diploma from “Ecole Nationale Supérieure de Chimie de Strasbourg” (France)
Ph.D. (1984, University of Paris VI)
Post-doctoral fellow (University of California, Berkeley, CA USA, Département de Chimie, lab. P.A. Bartlett)
researche Associate CNRS (1981) then Research Scientist (1982-1999) and Senior Research Scientist of CNRS.

Francine C. Acher is a CNRS Research Director leading the “Medicinal Chemistry for the Modulation of Synaptic Transmission” group. She received her Ph.D. in Chemistry from the University of Paris-VI in 1984 and pursued postdoctoral research at the department of Chemistry at University of California Berkeley with Prof. P.A. Bartlett. All through her carrier, F. Acher has been involved in the design and synthesis of non-natural amino acids and the investigation of their roles in various biological systems mostly in the CNS. She developed a specific expertise in molecular modeling in close interaction with biology allowing her major achievements in receptor activation mechanism and virtual high throughput screening as well as proof of concept in the validation of therapeutic targets. Her interdisciplinary research was made possible by close interaction with collaborators in different fields such as pharmacology, molecular biology and behavior. She has published 126 articles in peer reviewed journals and book chapters (h-index 32) and filed 10 international patents
F. Acher has been involved in the design of mGluR ligands since the discovery of aminocyclopentane dicarboxylic acid (ACPD) the first selective agonist in the early nineties. She discovered some potent group-III selective agonists such as ACPT-I, commercially available, and LSP1-2111, LSP4- 2022 and LSP2-9166. She took part to the evaluation of these compounds in several behaviour studies in animal models of Parkinson’s disease, pain, psychiatric disorders, addiction and epilepsy. Molecular modeling including generation of 3D-homology models, virtual high throughput screening and hit identification was a key asset in these outcomes

Research Interest

Bioorganic chemistry, Amino acids, Drug design, Relation of conformation to biological activity, Molecular recognition, Molecular modeling: pharmacophore models, homology modeling, dockings, virtual screening, de novo design, Amino acid receptors / glutamate receptors and transporters, G-protein coupled receptors of class C.

Key words:

Orthosteric ligands, transporter inhibitors, glutamate, probe synthesis, structure-activity relationship, small molecule-protein interaction, structure function studies, docking, virtual high throughput screening, hit optimization.

 

 

Research

The group is focused on small molecules that target receptors and transporters of synaptic transmission and their mechanisms. Using synthetic organic chemistry and molecular modeling, we develop pharmacological and therapeutic tools and investigate receptor activation and neurotransmitter transport. The team is involved in various projects from the initial design (molecules, 3D models…) all along to the in vivo studies. The interdisciplinary projects are made possible through numerous collaborations in the fields of pharmacology, molecular biology, cellular biology and behavior. Thus, molecules that are developed in the group allow investigations of animal models of Parkinson’s disease motor symptoms, psychiatric diseases, epilepsy, cognition, pain and addiction as well as imaging and activation or transport mechanism elucidation. Our research spans over two major fields that are actually linked in the synaptic event: Class C G Protein Coupled Receptors (GPCRs) and neuronal transporters. More recently, we initiated with the Metabolism group, the Tryptophan metabolism project based on our experience with cinnabarinic acid and its effect on metabotropic glutamate receptor 4.

Key words:
selective orthosteric ligands, transporter inhibitors, glutamate, probe synthesis, structure-activity relationship, small molecule-protein interaction, structure function studies, docking, virtual high throughput screening, hit optimization.

 

Collaborations

  • Dr J.-P. PIN Institute for Functional Genomics, Molecular Pharmacology Department, Montpellier, France
  • Dr H.-O. BERTRAND and GOUPIL-LAMY Biovia/Dassault Systems, Velizy , France
  • Dr J. WIERONSKA and A. PILC, Institute of Pharmacology, Krakow, Poland
  • Dr F. BERTASO, Institute for Functional Genomics, Montpellier, France
  • Dr F. FAZIO and N. NICOLETTI, Physiology and Pharmacology, Neuromed, Pozzilli, Italy
  • Dr L. MONY and Dr P. PAOLETTI, Laboratoire de Neurobiologie, Ecole Normale Supérieure, Paris, France
  • Dr B. GASNIER CNRS University Paris Descartes, France
  • Dr N. MARIE and Dr F. NOBLE CNRS University Paris Descartes, France
  • Dr J.-P. MOTHET, Univ Paris Saclay, France
  • Dr R. NGOMBA University of Lincoln, UK
  • Pr P. FLOR, University of Regensburg, Germany
  • Dr M. BLANCHARD-DESCE, University of Bordeaux, France
  • Dr A. LLEBARIA Institute of Advanced Chemistry of Catalonia (IQAC), Barcelona, Spain
  • Pr U. ISACOFF University of California Berkeley (USA)

 Science Outreach

 Épilepsie : une nouvelle piste thérapeutique identifiée

Molecular discovery at Université de Paris could improve treatment for Parkinson’s patients

Portraits of Sustainability Pioneers: Dassault Systèmes presents Francine Acher of Univ. de Paris

Recent Publications

2020

(1) A. Mikou, A. Cabayé, A. Goupil, H.-O. Bertrand, J.-P. Mothet, F. Acher
Asc-1 Transporter (SLC7A10): Homology models and molecular dynamics insights into the first steps of the transport mechanism. Sci.Rep. DOI: doi.org/10.1038/s41598-020-60617-y

(2)Poirel O, Mamer LE, Herman MA, Arnulf-Kempcke M, Kervern M, Potier B, Miot S, Wang J, Favre-Besse FC, Brabet I, Laras Y, Bertrand HO, Acher F, Pin JP, Puel JL, Giros B, Epelbaum J, Rosenmund C, Dutar P, Daumas S, El Mestikawy S, Pietrancosta N. LSP5-2157 a new inhibitor of vesicular glutamate transporters. Neuropharmacology. 2020 Mar 1;164:107902. doi: 10.1016/j.neuropharm.2019.107902.

2019

(1) B. Girard, P. Tuduri, M. P. Moreno, S. Sakkaki, C. Barboux, T.Bouschet, A. Varrault, J. Vitre, I. McCort, J. Dairou, F. Acher, L. Fagni, N. Marchi, J. Perroy, F. Bertaso The mGlu7 receptor provides new protective effects against epileptogenesis and epileptic seizures. Neurobiology of disease 2019, 129, 13-28. doi: 10.1016/j.nbd.2019.04.016.

(2) Maya Kansara, Kristian Thomson, Puiyi Pang, Aurelie Dutour, Lisa Mirabello, Francine Acher, Jean-Philippe Pin, Michele W.L. Teng, Juming Yan, Mark J. Smyth, David M. Thomas. Infiltrating Myeloid Cells Drive Osteosarcoma Progression via GRM4 Regulation of IL23. Cancer Discovery 2019, 9(11):1511-1519; doi: 10.1158/2159-8290.CD-19-0154.

(3) Orrico-Sanchez A., Chausset-Boissarie L., Alves de Sousa R., Coutens B., Rezai Amin S., Vialou V., Louis F., Hessani A., Dansette P.M., Zornoza T., Gruszczynski C., Giros B., Guiard B.P., Acher F., Pietrancosta N., Gautron S. Antidepressant efficacy of a selective organic cation transporter blocker in a mouse model of depression. Mol Psychiatry 2019 doi: 10.1038/s41380-019-0548-4. [Epub ahead of print]

(4) Habrian C., Levitz J., Vyklicky V., Fu Z., Hoagland A., McCort-Tranchepain I., Acher F. and Isacoff E. Y. Novel conformational pathway provides unique sensitivity and dynamics to a synaptic mGluR. Nature Commun 2019, 10(1):5572. doi: 10.1038/s41467-019-13407-8.

2018

(1) Zussy, C.; Gómez-Santacana, X.; Rovira, X.; De Bundel, D.; Ferrazzo, S.; Bosch, D.; Asede, D.; Malhaire, F.; Acher, F.; Giraldo, J.; Valjent, E.; Ehrlich, I.; Ferraguti, F.; Pin, J.-P.; Llebaria, A.; Goudet, C. Dynamic modulation of inflammatory pain-related affective and sensory symptoms by optical control of amygdala metabotropic glutamate receptor 4. Mol Psychiatry 2018, 23, 509-520. doi: 10.1038/mp.2016.223.

(2) Hajasova, Z., Canestrelli, C., Acher, F., Noble F., Marie N., Role of mGlu7 receptor in morphine rewarding effects is uncovered by a novel orthosteric agonist. Neuropharmacology 2018, 131, 424-430.

(3) Lebourgeois S., Vilpoux C., Acher F., Marie N., Noble F., Naassila M. Pharmacological activation of mGluR4 and mGluR7, by LSP2-9166, reduces ethanol consumption and relapse in rat. Neuropharmacology 2018, 133, 163-170. doi: 10.1016/j.neuropharm.2018.01.031

(4) Selvam, C., Lemasson, I. A., Brabet, I., Oueslati, N., Karaman, B., Cabaye, A., Tora, A. S., Commare, B., Courtiol, T., Cesarini, S., McCort-Tranchepain, I., Rigault, D., Mony, L., Bessiron, T., McLean, H., Leroux, F. R., Colobert, F., Daniel, H. Goupil-Lamy, A., Bertrand, H.-O., Goudet, C., Pin, J.-P. and Acher, F. C. Increased potency and selectivity for group-III metabotropic glutamate receptor agonists binding at dual sites. J Med Chem 2018, 61, 1969-1989. doi: 10.1021/acs.jmedchem.7b01438

(5) Goudet, C.; Rovira, X.; Rondard, P.; Pin, J.-P.; Llebaria, A.; Acher, F. Modulation of Metabotropic Glutamate Receptors by Orthosteric, Allosteric, and Light-Operated Ligands. Springer International Publishing AG: 2018; p 32.

(6) Cieślik, P., Woźniak, M., Rook, J.M., Tantawy, M.N., Conn, P.J., Acher, F., Tokarski, K., Kusek, M., Pilc, A., Wierońska, J.M. Mutual activation of glutamatergic mGlu4 and muscarinic M4 receptors reverses schizophrenia related changes in rodents. Psychopharmacology 2018, 235(10), 2897-2913 doi: 10.1007/s00213-018-4980-y.

(7) Belhocine A, Veglianese P, Hounsou C, Dupuis E, Acher F, Durroux T, Goudet C, Pin JP. Profiling of orthosteric and allosteric group-III metabotropic glutamate receptor ligands on various G protein-coupled receptors with Tag-lite® assays. Neuropharmacology 2018, 140, 233-245; doi: 10.1016/j.neuropharm.2018.07.032.

(8) Tora AS, Rovira X, Cao AM, Cabayé A, Olofsson L, Malhaire F, Scholler P, Baik H, Van Eeckhaut A, Smolders I, Rondard P, Margeat E, Acher F, Pin JP, Goudet C. Chloride ions stabilize the glutamate-induced active state of the metabotropic glutamate receptor 3. Neuropharmacology 2018, 140, 275-286; doi: 10.1016/j.neuropharm.2018.08.011.

2017

(1) Smith N, Pietrancosta N, Davidson S, Dutrieux J, Chauveau L, Cutolo P, Dy M, Scott-Algara D, Manoury B, Zirafi O, McCort-Tranchepain I, Durroux T, Bachelerie F, Schwartz O, Münch J, Wack A, Nisole S, Herbeuval JP. Natural amines inhibit activation of human plasmacytoid dendritic cells through CXCR4 engagement. Nat Commun. 2017 Feb 9;8:14253. doi: 10.1038/ncomms14253.

(2) Woźniak M, Gołembiowska K, Noworyta-Sokołowska K, Acher F, Cieślik P, Kusek M, Tokarski K, Pilc A, Wierońska JM. Neurochemical and behavioral studies on the 5-HT1A-dependent antipsychotic action of the mGlu4 receptor agonist LSP4-2022. Neuropharmacology 2017, 115, 149-165.

2016

(1) Tassin, V.; Girard, B.; Chotte ,A.; Fontanaud, P.; Rigault, D.; Kalinichev, M.; Perroy, J.; Acher, F.; Fagni, L. and Bertaso, F. Phasic and Tonic mGlu7 Receptor Activity Modulates the Thalamocortical Network. Frontiers in neural circuits 2016, 31, article number 31.

(2) Wozniak, M.; Wieronska, J. M.; Acher, F.; Marciniak, M.; Lason-Tyburkiewicz, M.; Gruca, P.; Papp, M. and Pilc, A. Involvement of GABAB signaling in the Antipsychotic-like Action of the Novel Orthosteric Agonist of mGlu4 Receptor, LSP4-2022. Cur Neuropharmacology 2016, 14(5), 413-426.

For older See PubMed