SPPIN - Saints-Pères Paris Institute for the Neurosciences - CNRS UMR 8003
Université Paris Cité
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
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.
Orthosteric ligands, transporter inhibitors, glutamate, probe synthesis, structure-activity relationship, small molecule-protein interaction, structure function studies, docking, virtual high throughput screening, hit optimization.
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.
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.
- 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)
- Metabotropic glutamate receptor orthosteric ligands and their binding sites.
Acher FC, Cabayé A, Eshak F, Goupil-Lamy A, Pin JP : Neuropharmacology, 2022
- A nanobody activating metabotropic glutamate receptor 4 discriminates between homo- and heterodimers.
Haubrich J, Font J, Quast RB, Goupil-Lamy A, Scholler P, Nevoltris D, Acher F, Chames P, Rondard P, Prézeau L, Pin JP : Proc Natl Acad Sci U S A, 2021
- LSP2-9166, an orthosteric mGlu4 and mGlu7 receptor agonist, reduces cocaine self-administration under a progressive ratio schedule in rats.
De Sa Nogueira D, Bourdy R, Filliol D, Quessada C, McCort-Tranchepain I, Acher F, Zwiller J, Romieu P, Befort K : Neurosci Lett, 2021
- Antidepressant efficacy of a selective organic cation transporter blocker in a mouse model of depression.
Orrico-Sanchez A, Chausset-Boissarie L, Alves de Sousa R, Coutens B, Rezai Amin S, Vialou V, Louis F, Hessani A, Dansette PM, Zornoza T, Gruszczynski C, Giros B, Guiard BP, Acher F, Pietrancosta N, Gautron S : Mol Psychiatry, 2020
- Illuminating the allosteric modulation of the calcium-sensing receptor.
Liu H, Yi P, Zhao W, Wu Y, Acher F, Pin JP, Liu J, Rondard P : Proc Natl Acad Sci U S A, 2020
- LSP5-2157 a new inhibitor of vesicular glutamate transporters.
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 : Neuropharmacology, 2020
- Asc-1 Transporter (SLC7A10): Homology Models And Molecular Dynamics Insights Into The First Steps Of The Transport Mechanism.
Mikou A, Cabayé A, Goupil A, Bertrand HO, Mothet JP, Acher FC : Sci Rep, 2020
- Amino Acids Bearing Aromatic or Heteroaromatic Substituents as a New Class of Ligands for the Lysosomal Sialic Acid Transporter Sialin.
Dubois L, Pietrancosta N, Cabaye A, Fanget I, Debacker C, Gilormini PA, Dansette PM, Dairou J, Biot C, Froissart R, Goupil-Lamy A, Bertrand HO, Acher FC, McCort-Tranchepain I, Gasnier B, Anne C : J Med Chem, 2020
- Conformational pathway provides unique sensitivity to a synaptic mGluR.
Habrian CH, Levitz J, Vyklicky V, Fu Z, Hoagland A, McCort-Tranchepain I, Acher F, Isacoff EY : Nat Commun, 2019
- Infiltrating Myeloid Cells Drive Osteosarcoma Progression via GRM4 Regulation of IL23.
Kansara M, Thomson K, Pang P, Dutour A, Mirabello L, Acher F, Pin JP, Demicco EG, Yan J, Teng MWL, Smyth MJ, Thomas DM : Cancer Discov, 2019
- The mGlu7 receptor provides protective effects against epileptogenesis and epileptic seizures.
Girard B, Tuduri P, Moreno MP, Sakkaki S, Barboux C, Bouschet T, Varrault A, Vitre J, McCort-Tranchepain I, Dairou J, Acher F, Fagni L, Marchi N, Perroy J, Bertaso F : Neurobiol Dis, 2019
- Chloride ions stabilize the glutamate-induced active state of the metabotropic glutamate receptor 3.
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 : Neuropharmacology, 2018
- Profiling of orthosteric and allosteric group-III metabotropic glutamate receptor ligands on various G protein-coupled receptors with Tag-lite assays.
Belhocine A, Veglianese P, Hounsou C, Dupuis E, Acher F, Durroux T, Goudet C, Pin JP : Neuropharmacology, 2018
- Mutual activation of glutamatergic mGlu and muscarinic M receptors reverses schizophrenia-related changes in rodents.
Cieślik P, Woźniak M, Rook JM, Tantawy MN, Conn PJ, Acher F, Tokarski K, Kusek M, Pilc A, Wierońska JM : Psychopharmacology (Berl), 2018
- Dynamic modulation of inflammatory pain-related affective and sensory symptoms by optical control of amygdala metabotropic glutamate receptor 4.
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 JP, Llebaria A, Goudet C : Mol Psychiatry, 2018
- Increased Potency and Selectivity for Group III Metabotropic Glutamate Receptor Agonists Binding at Dual sites.
Selvam C, Lemasson IA, Brabet I, Oueslati N, Karaman B, Cabaye A, Tora AS, Commare B, Courtiol T, Cesarini S, McCort-Tranchepain I, Rigault D, Mony L, Bessiron T, McLean H, Leroux FR, Colobert F, Daniel H, Goupil-Lamy A, Bertrand HO, Goudet C, Pin JP, Acher FC : J Med Chem, 2018
- Pharmacological activation of mGlu4 and mGlu7 receptors, by LSP2-9166, reduces ethanol consumption and relapse in rat.
Lebourgeois S, Vilpoux C, Jeanblanc J, Acher F, Marie N, Noble F, Naassila M : Neuropharmacology, 2018
- Role of mGlu7 receptor in morphine rewarding effects is uncovered by a novel orthosteric agonist.
Hajasova Z, Canestrelli C, Acher F, Noble F, Marie N : Neuropharmacology, 2018
- Neurochemical and behavioral studies on the 5-HT-dependent antipsychotic action of the mGlu receptor agonist LSP4-2022.
Woźniak M, Gołembiowska K, Noworyta-Sokołowska K, Acher F, Cieślik P, Kusek M, Tokarski K, Pilc A, Wierońska JM : Neuropharmacology, 2017
- Involvement of GABAB Receptor Signaling in Antipsychotic-like Action of the Novel Orthosteric Agonist of the mGlu4 Receptor, LSP4-2022.
Woźniak M, Acher F, Marciniak M, Lasoń-Tyburkiewicz M, Gruca P, Papp M, Pilc A, Wierońska JM : Curr Neuropharmacol, 2016
- Phasic and Tonic mGlu7 Receptor Activity Modulates the Thalamocortical Network.
Tassin V, Girard B, Chotte A, Fontanaud P, Rigault D, Kalinichev M, Perroy J, Acher F, Fagni L, Bertaso F : Front Neural Circuits, 2016
- Determination of the absolute configuration of phosphinic analogues of glutamate
Commare B, Rigault D, Lemasson IA, Deschamps P, Tomas A, Roussel P, Brabet I, Goudet C, Pin JP, Leroux FR, Colobert F, Acher FC : Org Biomol Chem, 2015
- Two-photon caging groups: effect of position isomery on the photorelease properties of aminoquinoline-derived photolabile protecting groups
Tran C, Gallavardin T, Petit M, Slimi R, Dhimane H, Blanchard-Desce M, Acher FC, Ogden D, Dalko PI : Org Lett, 2015
- Design, synthesis and biological evaluation of small-azo-dyes as potent Vesicular Glutamate Transporters inhibitors.
Favre-Besse FC, Poirel O, Bersot T, Kim-Grellier E, Daumas S, El Mestikawy S, Acher FC, Pietrancosta N : Eur J Med Chem, 2014
- Molecular determinants of agonist selectivity in glutamate-gated chloride channels which likely explain the agonist selectivity of the vertebrate glycine and GABAA-ρ receptors.
Blarre T, Bertrand HO, Acher FC, Kehoe J : PLoS One, 2014
- Tandem triad systems based on FRET for two-photon induced release of glutamate.
Picard S, Cueto-Diaz EJ, Genin E, Clermont G, Acher F, Ogden D, Blanchard-Desce M : Chem Commun (Camb), 2013
- Variations on glutamate binding in channel-gated receptors.
Acher FC : Structure, 2013
- The antipsychotic-like effects of the mGlu group III orthosteric agonist, LSP1-2111, involves 5-HT1A signalling.
Wierońska JM, Acher FC, Sławińska A, Gruca P, Lasoń-Tyburkiewicz M, Papp M, Pilc A : Psychopharmacology, 2013
- Substitution effect on the one- and two-photon sensitivity of DMAQ
Petit M, Tran C, Roger T, Gallavardin T, Dhimane H, Palma-Cerda F, Blanchard-Desce M, Acher FC, Ogden D, Dalko PI : Org Lett, 2012
- Opposing efficacy of group III mGlu receptor activators, LSP1-2111 and AMN082, in animal models of positive symptoms of schizophrenia.
Wierońska JM, Stachowicz K, Acher F, Lech T, Pilc A : Psychopharmacology, 2012
- A novel selective metabotropic glutamate receptor 4 agonist reveals new possibilities for developing subtype selective ligands with therapeutic potential.
Goudet C, Vilar B, Courtiol T, Deltheil T, Bessiron T, Brabet I, Oueslati N, Rigault D, Bertrand HO, McLean H, Daniel H, Amalric M, Acher F, Pin JP : FASEB J, 2012
- Cinnabarinic acid, an endogenous metabolite of the kynurenine pathway, activates type 4 metabotropic glutamate receptors.
Fazio F, Lionetto L, Molinaro G, Bertrand HO, Acher F, Ngomba RT, Notartomaso S, Curini M, Rosati O, Scarselli P, Di Marco R, Battaglia G, Bruno V, Simmaco M, Pin JP, Nicoletti F, Goudet C : Mol Pharmacol, 2012
- Successful prediction of substrate-binding pocket in SLC17 transporter sialin.
Pietrancosta N, Anne C, Prescher H, Ruivo R, Sagné C, Debacker C, Bertrand HO, Brossmer R, Acher F, Gasnier B : J Biol Chem, 2012
- Orthosteric versus allosteric GPCR activation: the great challenge of group-III mGluRs.
Flor PJ, Acher FC : Biochem Pharmacol, 2012
- Group III and subtype 4 metabotropic glutamate receptor agonists: discovery and pathophysiological applications in Parkinson's disease.
Amalric M, Lopez S, Goudet C, Fisone G, Battaglia G, Nicoletti F, Pin JP, Acher FC : Neuropharmacology, 2012
- Role of mGluR4 in acquisition of fear learning and memory.
Davis MJ, Iancu OD, Acher FC, Stewart BM, Eiwaz MA, Duvoisin RM, Raber J : Neuropharmacology, 2012
- Synthesis of quinoline dicarboxylic esters as biocompatible fluorescent tags.
Laras Y, Hugues V, Chandrasekaran Y, Blanchard-Desce M, Acher FC, Pietrancosta N : J Org Chem, 2012
- A critical pocket close to the glutamate binding site of mGlu receptors opens new possibilities for agonist design.
Acher FC, Selvam C, Pin JP, Goudet C, Bertrand HO : Neuropharmacology, 2011
- Rose Bengal analogs and vesicular glutamate transporters (VGLUTs)
Pietrancosta N, Kessler A, Favre-Besse F-C, Triballeau N, Quentin T, Giros B, El Mestikawy S, Acher F C : Bioorganic \& medicinal chemistry, 2010
- Identification of a novel NR2B-selective NMDA receptor antagonist using a virtual screening approach
Mony L, Triballeau N, Paoletti P, Acher F C, Bertrand H-O : Bioorganic \& medicinal chemistry letters, 2010
- A virtual screening hit reveals new possibilities for developing group III metabotropic glutamate receptor agonists
Selvam C, Oueslati N, Lemasson IA, Brabet I, Rigault D, Courtiol T, Cesarini S, Triballeau N, Bertrand HO, Goudet C, Pin JP, Acher FC : J Med Chem, 2010
- Aplysia cys-loop glutamate-gated chloride channels reveal convergent evolution of ligand specificity
Kehoe J, Buldakova S, Acher F, Dent J, Bregestovski P, Bradley J : J Mol Evol, 2009
- High-potency olfactory receptor agonists discovered by virtual high-throughput screening: molecular probes for receptor structure and olfactory function
Triballeau N, Van Name E, Laslier G, Cai D Paillard G Sorensen PW, Hoffmann R, Bertrand HO, Ngai J, Acher FC : Neuron, 2008
- Modulation of Metabotropic Glutamate Receptors by Orthosteric, Allosteric, and Light-Operated Ligands
Goudet C, Rovira X, Rondard P, Pin J-P, Llebaria A, Acher F : extracted from Structure and Function of GPCRs Guillaume Lebon - Springer, pages 253-284, ISBN:978-3-030-24589-4, 2019