Brain Biology and Chemistry

Presentation

« Brain Biology & Chemistry » team belongs to the « Lille Neuroscience & Cognition » research center and is located in Lille, France.

The team is composed of an Inserm researcher, eleven professors and associate professors, two hospital practitioners. It benefits from the technical support of seven people and welcomes many students: from master degree, PhD students to post-doc fellows.
Our multidisciplinary team brings together chemists, biologists and spectroscopists.

NEWS

  • STAFF
  • RESEARCH INTEREST
  • PUBLICATIONS

Associate Professors/Professors – University-Associated

Patricia Melnyk
Professor of Physical Chemistry
University of Lille, UFR3S, School of Pharmacy
Teaching : Physical chemistry, Medicinal chemistry
Research : medchem, hit-to-lead, molecular interactions, drug development
Laurence Agouridas, PhD
Associate Professor
University of Lille, UFR3S, School of Pharmacy
Teaching : Physical chemistry, Medicinal chemistry
Research : Photochemistry, photo-switches, synthesis, protein agregation
Fabrice Bailly, PhD
Associate Professor
University of Lille, Faculty of Sciences & Technologies
Teaching : Organic chemistry
Research : Medicinal chemistry, Molecular interactions ligand/protein, TEAD
Jérôme Berthet, PhD
Associate Professor
University of Lille, UFR3S, School of Pharmacy
Teaching : Biophysics, NMR
Research : Photochemistry, NMR, photo-switches
Marie-Christine Chartier-Harlin, PhD
INSERM Research Professor
University of Lille, UFR3S, School of Medecine
Teaching : Neurosciences & genetics
Research : Neurodegenerative diseases, Omics, physiopathology, cellular and animal models, SNCA, LRRK2, cellular trafficking
Philippe Cotelle, PhD
Professor of Organic Chemistry
Centrale Lille, ENSCL
Teaching : Organic chemistry
Recherche : Medicinal chemistry, TEAD ligands
Stéphanie Delbaere, PhD
Professor of Biophysics, Assessor in charge of ressources and staff
University of Lille, UFR3S, School of Pharmacy
Teaching : Biophysics, NMR
Research : Photochemistry, NMR, photo-switches
Jamal El Bakali, PhD
Associate Professor
University of Lille, UFR3S, School of Pharmacy
Teaching : Medicinal Chemistry
Research : Medicinal Chemistry
Nicolas Lebègue, PhD
Professor of Medicinal chemistry
University of Lille, UFR3S, School of Pharmacy
Teaching : Medicinal Chemistry
Research :
Molecular interactions, Medicinal Chemistry, Protein-protein inhibitors, LRRK2, SIRT1, PPAR, tubuline
Maxime Liberelle, PhD
Associate Professor
University of Lille, UFR3S, School of Pharmacy
Teaching :
Biophysics
Research :
MUC4, MST, Molecular interactions, Medicinal Chemistrt, Protein-protein inhibitors, LRRK2
Séverine Ravez, PhD
Associate Professor
University of Lille, UFR3S, School of Pharmacy
Teaching : Medicinal Chemistry
Research :
Biochemistry, Enzymology, Screening, Ferroptose, Medicinal Chemistry
Jean-Marc Taymans, PhD
Associate Professor (HDR Docent)
University of Lille, UFR3S, School of Medecine
Teaching : Neurosciences
Research :
Molecular and Cellular Neuroscience, LRRK2, experimental models of Parkinson's disease
Said Yous, PhD
Associate Professor (HDR Docent)
University of Lille, UFR3S, School of Pharmacy
Teaching : Medicinal chemistry
Research :
Medicinal chemistry, melatonine ligands, A2A antagonists
Eugénie Mutez, PhD
Lille Hospital
Activity : Neurologist, movement’s pathologies, Parkinson’s disease, clinical studies, physiopathology and therapeutics
Clémence Simonin, PhD
Lille Hospital
Activity :
Neurologist, movement’s pathologies, Huntington ’s disease, clinical studies, physiopathology and therapeutics

Research support staff

Mathilde Coevoet
Engineer assistant, UFR3S, University of Lille
Staelle Corvo-Chamaillard
Engineer assistant, INSERM
Paul-Emmanuel Larchanché
Technician, UFR3S, University of Lille
Bénédicte Vanteghem-Oxombre
Engineer, UFR3S, University of Lille

Yanisse Boulesnane
Engineer

Claire Deldycke
Engineer

Coline Leghay, PhD
Engineer

Laurine Vandewynckel
Engineer

Research post-doctoral fellows

Benjamin Zagiel, PhD
ATER, University of Lille, UFR3S, School of Pharmacy
Teaching : Chemistry
Research : TEAD

PhD students

Antoine Marchand

Alessia Sarchione

 

Florine Toulotte
Adriana Figueroa-Garcia
Liesel Mary Goveas

Pasquale Sileo

 

Nicolas STOUP

 

Alexandre Gobert
The MUC4-ErbB2 complex: from the structure-function relationship towards therapeutic targeting 
Amélie Laversin
Design, synthesis and evaluation of potential A2A receptor antagonists and dual ligands targeting A2A / mGlu5 receptors in the treatment of neurodegenerative diseases
Justine Peters
Design, synthesis and pharmacological evaluation of new antimalarial compounds

Alumni

Marie Tautou
PhD

William Sibran
Engineer
Guillaume Patient
PhD
Anne-Sophie Journé, PhD
Engineer SATT

Alice Ameryckx, PhD
Post Doc

Raphaël BOLTEAU
PhD

Alice Thiry
Assistant engineer

Amélie Vizeneux
Engineer

Fahima Madouri, PhD
Engineer SATT

Tarak Saied, PhD
ATER

Catherine BAUD, PhD
Post Doc

Samantha Ploegaerts
Management assistant
Florian DESCAMPS
PhD
Manon STURBAUT
PhD
Nathalie FLOUQUET
Engineer
Pascal CARATO, PhD
Assistant Professor
Noémie DEGUINE
Assistant Engineer
Mohsine DRIOWYA, PhD
ATER
Véronique LECLERC, PhD
Engineer
Christophe MESANGEAU, PhD
Post Doc
Valeria MOAS-HÉLOIRE
PhD
Camille QUENON
M2
Angela RINCON-ARIAS
PhD
Ayano TANAKA-SLIWA
Management assistant
Aurélien TOURTEAU, PhD
ATER
Bao VY LAM, PhD
ATER

Romain Duroux
PhD

Floriane Gibault
PhD

Rajaa BOULAHJAR, PhD
Engineer SATT
The drug discovery process, from fundamental biology to the discovery of drug candidates, highlights the expertise of our team.

Neurodegenerative diseases are characterized by common biological hallmarks such as inflammation, aggregation of altered proteins, modification of cell and vesicular trafficking, cellular (or neuronal) degeneration leading to cognitive impairments. We want to design and caracterize new molecules active on these hallmarks. To do this, we have identified targets of interest on which we are focusing our efforts and we will continue to define relevant targets using Omics approaches on patient samples. New emerging targets are under studying.

More specifically, we are studying targets linked to defects in cell trafficking and their involvement in protein homeostasis, such as LRRK2 or alpha synuclein for the treatment of Parkinson's disease, the Hippo pathway in Huntington's disease or sigma-1 for the treatment of Multiple Sclerosis. Then we develop the evaluation tests (enzymatic, biophysical or cellular methods) and test collections of compounds. Molecular modeling and medicinal chemistry allow us to optimize the compounds and go from hits to leads. Of greatest interest in neurodegenerative diseases is the study of modulators of protein-protein interactions. For instance, we are developing TEAD modulators or photo-switchable compounds capable of destroying protein aggregates. Autophagy modulating compounds are being studied for the treatment of Alzheimer's disease. One of these compounds is now in phase 2. Pharmacological studies and ADME Tox provide drug candidates.

Publications

2021

Domenighetti C, Sugier PE, Sreelatha AAK, Schulte C, Grover S, Mohamed O, Portugal B, May P, Bobbili DR, Radivojkov-Blagojevic M, Lichtner P, Singleton AB, Hernandez DG, Edsall C, Mellick GD, Zimprich A, Pirker W, Rogaeva E, Lang AE, Koks S, Taba P, Lesage S, Brice A, Corvol JC, Chartier-Harlin MC, Mutez E, Brockmann K, Deutschländer AB, Hadjigeorgiou GM, Dardiotis E, Stefanis L, Simitsi AM, Valente EM, Petrucci S, Duga S, Straniero L, Zecchinelli A, Pezzoli G, Brighina L, Ferrarese C, Annesi G, Quattrone A, Gagliardi M, Matsuo H, Kawamura Y, Hattori N, Nishioka K, Chung SJ, Kim YJ, Kolber P, van de Warrenburg BP, Bloem BR, Aasly J, Toft M, Pihlstrøm L, Guedes LC, Ferreira JJ, Bardien S, Carr J, Tolosa E, Ezquerra M, Pastor P, Diez-Fairen M, Wirdefeldt K, Pedersen NL, Ran C, Belin AC, Puschmann A, Hellberg C, Clarke CE, Morrison KE, Tan M, Krainc D, Burbulla LF, Farrer MJ, Krüger R, Gasser T, Sharma M, Elbaz A,
Comprehensive Unbiaised Risk Factor Assessment for Genetics and Environment in Parkinson’s Disease (Courage-PD) consortium. Mendelian Randomisation Study of Smoking, Alcohol, and Coffee Drinking in Relation to Parkinson's Disease.J Parkinsons Dis. 2021

Ettaoussi M, Laversin A, Vreulz B, Rami M, Lebègue N, Delagrange P, Caignard D-H, Melnyk P, Liberelle M, Yous S,
Synthesis and SAR studies of Novel Isoquinoline and Tetrahydroisoquinoline Derivatives as Melatonin Receptor Ligands, Chem Med Chem, 2021, accepté

Marc S, Mésangeau C, Coevoet M, Barczyk A, Burlet S, Verwaerde P, Brantis C, Sergeant N, Carato P, Melnyk P,
Pharmacomodulations around an anti-Alzheimer drug-candidate, Eur J Med Chem Rep, 2021, accepté

Pacot L, Vidaud D, Sabbagh A, Laurendeau I, Briand-Suleau A, Coustier A, Maillard T, Barbance C, Morice-Picard F, Sigaudy S, Glazunova OO, Damaj L, Layet V, Quelin C, Gilbert-Dussardier B, Audic F, Dollfus H, Guerrot AM, Lespinasse J, Julia S, Vantyghem MC, Drouard M, Lackmy M, Leheup B, Alembik Y, Lemaire A, Nitschké P, Petit F, Dieux Coeslier A, Mutez E, Taieb A, Fradin M, Capri Y, Nasser H, Ruaud L, Dauriat B, Bourthoumieu S, Geneviève D, Audebert-Bellanger S, Nizon M, Stoeva R, Hickman G, Nicolas G, Mazereeuw-Hautier J, Jannic A, Ferkal S, Parfait B, Vidaud M, Members Of The Nf France Network, Wolkenstein P, Pasmant E.
Severe Phenotype in Patients with Large Deletions of NF1, Cancers (Basel). 2021, 13(12), 2963.

Sarchione A, Marchand A, Taymans JM, Chartier-Harlin MC.
Alpha-Synuclein and Lipids: The Elephant in the Room?, Cells. 2021, 10(9), 2452.

Shabajee-Alibay P, Bonnaud A, Malpaux B, Delagrange P, Audinot V, Yous S, Boutin JA, Stephan J-P, Leprince J, Legros C,
Putative new melatonin binding site in sheep brain, MTx: preliminary observations and characteristics
J Pharmacol Exp Therap, 2021, accepté

Stoup N, Liberelle M, Schulz C, Cavdarli S, Vasseur R, Magnez R, Lahdaoui F, Skrypek N, Peretti F, Frenois F, Thuru X, Melnyk P, Renault N, Jonckherre N, Lebegue N, Van Seuningen I,
The EGF domains of MUC4 oncomucin mediate HER2 binding affinity and promote pancreatic cancer cell tumorigenesis, Cancers, 2021, sous presse.

Sturbaut M, Bailly F, Coevoet M, Pugniere M, Liberelle M, Magnez R, Thuru X, Melnyk P, Gelin M, Allemand F, Guichou JF, Cotelle P.
Discovery of a cryptic site at the interface 2 of TEAD – Toward new anti-cancer compounds, Eur J Med Chem, 2021, 226, 113835-849.

Taymans JM,
Specialty Grand Challenge for Molecular Signalling and Pathways in Molecular Neuroscience. Front Mol Neurosci. 2021, 14, 694776.

Cresto N, Gardier C, Gaillard MC, Gubinelli F, Roost P, Molina D, Josephine C, Dufour N, Auregan G, Guillermier M, Bernier S, Jan C, Gipchtein P, Hantraye P, Chartier-Harlin MC, Bonvento G, Van Camp N, Taymans JM, Cambon K, Liot G, Bemelmans AP, Brouillet E,
The C-Terminal Domain of LRRK2 with the G2019S Substitution Increases Mutant A53T α-Synuclein Toxicity in Dopaminergic, Neurons In Vivo, Int J Mol Sci, 2021 Jun 23;22(13):6760.

Drouyer M, Bolliger MF, Lobbestael E, Van den Haute C, Emanuele M, Lefebvre R, Sibran W, De Wit T, Leghay C, Mutez E, Dzamko N, Halliday GM, Murayama S, Martoriati A, Cailliau K, Bodart JF, Chartier-Harlin MC, Baekelandt V, Nichols RJ,
Taymans JM, Protein phosphatase 2A holoenzymes regulate leucine-rich repeat kinase 2 phosphorylation and accumulation, Neurobiol Dis, 2021 Sep;157:105426.

Goveas L, Mutez E, Chartier-Harlin MC, Taymans JM,
Mind the Gap: LRRK2 Phenotypes in the Clinic vs. in Patient Cells, Cells, 2021 Apr 22;10(5):981.

Fedorova OA, Arkhipova AN, Panchenko PA, Berthet J, Delbaere S, Minkovska S & al,
Fluorescent photochromic complex of 1,8-naphthalimide derivative and benzopyrane containing benzo-18-crown-6 ether, J Photochem Photobiol A-Chem, 2021, 405

Graca V, Berthet J, Sousa CM, Delbaere S, Coelho PJ, Synthesis of Vinylnaphthofurans and NMR Analysis of their Photoswitching, Eur J Org Chem, 2021, 13, 1979-1988.

Tautou M, Eddarkaoui S, Descamps F, Larchanché PE, El Bakali J, Goveas LM, Dumoulin M, Lamarre C, Blum D, Buée L, Melnyk P*, Sergeant N*,
A β-secretase modulator decreases Tau pathology and preserves short-term memory in a mouse model of neurofibrillary degeneration, Frontiers in Pharmacology, 2021,12, 679335.

Gibault F, Bailly F*, Sturbaut M, Coevoet M, Pugniez M, Magnez R, Thuru X, Melnyk P, Allemand F, Hong W, Pobbati A, Guichou JF, Cotelle P, Design,
Synthesis and Evaluation of a Series of 1,5-Diaryl-1,2,3-triazole-4-carbohydrazones as Inhibitors of the YAP-TAZ/TEAD Complex
, Chem Med Chem, 2021, 16 (18), 2823-2844.

Stoup N, Liberelle M, Schulz C, Vasseur R, Magnez R, Thuru X, Melnyk P, Renault N, Jonckherre N, Lebegue N*, Van Seuningen I*, The EGF domains of MUC4 oncomucin interact with ErbB2 and mediate tumorigenic activity of cancer cells represent new potential therapeutic targets, The FASEB Journal. 2021; 35.

2020

Mangone G, Bekadar S, Cormier-Dequaire F, Tahiri K, Welaratne A, Czernecki V, Pineau F, Karachi C, Castrioto A, Durif F, Tranchant C, Devos D, Thobois S, Meissner WG, Navarro MS, Cornu P, Lesage S, Brice A, Welter ML, Corvol JC,
Early cognitive decline after bilateral subthalamic deep brain stimulation in Parkinson's disease patients with GBA mutations.
Parkinsonism Relat Disord. 2020, 76, 56-62.

Bachoud-Lévi , AC on behalf the Multicentric Intracerebral Grafting in Huntington's Disease Group. Human Fetal Cell Therapy in Huntington's Disease: A Randomized, Multicenter, Phase II Trial.
Mov Disord. 2020, 35(8), 1323-1335.

Belarbi K, Cuvelier E, Bonte MA, Desplanque M, Gressier B, Devos D, Chartier-Harlin MC, Glycosphingolipids and neuroinflammation in Parkinson’s disease, Mol Neurodegener, 2020, 15, 59.

Bolteau R, Descamps F, Ettaoussi M, Caignard D-H, Delagrange P, Melnyk P, Yous S, Quinalozine and Phtalazine Derivatives as Novel Melantonin Receptor Ligands Analogues of Agomelatine, Eur J Med Chem, 2020, 189, 112078.

Desplanque M, Bonte MA, Gressier B, Devos D, Chartier-Harlin MC, Belarbi K, Trends in glucocerebrosides research: a systematic review, Front Physiology, 2020, 29, 11:558090.

El-Kashef H, Badr G, Abo El-Maali N, Sayed D, Melnyk P, Lebègue N, Abd El-Khalek R, Synthesis of a novel series of (Z)-3,5-disubstituted thiazolidine-2,4-diones as promising anti-breats cancer agents, Bioorg Chem, 2020, 96,103569.

Hamdi I, Buntinx G, Aloïse S, Tiwari A K, Delbaere S, Takeshita M, Cyclization Dynamics and competitive processes of photochromic perfluorocyclopentene dithienylethylene in solution, ChemPhysChem, 2020, 21, 2223-2229.

Hurtevent A, Le Naour M, Leclerc V, Carato P, Melnyk P, Hennuyer N, Staels B, Beucher-Gaudin M, Dacquet C, Lebegue N, 6-Benzoyl-benzothiazol-2-one as an important scaffold on the pharmacological profile of α-alkoxyphenylpropionic acid derived PPAR agonists, J Enzyme Inhib Med Chem, 2020, 35(1), 524-538.

Keo A, Mahfouz A, Ingrassia AMT, Meneboo JP, Villenet C, Mutez E, Comptdaer T, Lelieveldt BPF, Figeac M, Chartier-Harlin MC, van de Berg WDJ, van Hilten JJ, Reinders MJT, Transcriptomic signatures of brain regional vulnerability to Parkinson's disease, Commun Biol, 2020, 3(1),101.

Kreisler A, Simonin C, Degardin A, Mutez E, Defebvre L, Anatomy-guided injections of botulinum neurotoxin in neck muscles: how accurate is needle placement? Eur J Neurol, 2020, sous presse.

Leguen C, Mazzah A, Penhoat M, Melnyk P, Rolando C, Chausset-Boissarie L, Direct and regioselective fluorination of pyridylic and quinolinic C(sp3)-H bonds with selectfluor, Synthesis, 2020, 53 (06), 1157-1162.

Liberelle M, Jonckheere N, Melnyk P, Van Seuningen I, Lebegue N, EGF-containing membrane-bound Mucins : a hidden ErbB2 signaling pathway ? J Med Chem, 2020, 63(10), 5074-5088.

Lobbestael E, Van den Haute C, Macchi F, Taymans JM, Baekelandt V, Pathogenic LRRK2 requires secondary factors to induce cellular toxicity, Bioscience Rep, 2020, sous presse.

Marchand A, Drouyer M, Sarchione A, Chartier-Harlin MC, Taymans JM, LRRK2 Phosphorylation, More Than an Epiphenomenon, Front Neurosci, 2020, 14,527.

Norel L, Bernot K, Gendron F, Gould C, Roisnel T, Delbaere S, Le Guennic B, Jacquemin D, Rigaut S, Coordination-enhanced photochromism in dysprosium dinuclear complexes with photomodulated single-molecule magnet behavior, Chem2, 2020, 4, 2 (Open access chemistry)

Ribeiro JA, Hammer A, Libreros-Zúñiga GA, Chavez-Pacheco SM, Tyrakis P, de Oliveira GS, Kirkman T, El Bakali J, Rocco SA, Sforça ML, Parise-Filho R, Coyne AG, Blundell TL, Abell C, Dias MVB, Using a fragment-based approach to identify alternative chemical scaffolds targeting dihydrofolate reductase from Mycobacterium tuberculosis, ACS Infect Dis, 2020, 6(8),2192-2201.

Rideout HJ, Chartier-Harlin MC, Fell MJ, Hirst WD, Huntwork-Rodriguez S, Leyns CEG, Mabrouk OS, Taymans JM, The Current State-of-the Art of LRRK2-Based Biomarker Assay Development in Parkinson's Disease, Front Neurosci, 2020, 14, 865.

Spillier Q, Ravez S, Unterlass J, Corbet C, Degavre C, Feron O, Frédérick R, Structure-Activity Relationships (SARs) of α-Ketothioamides as Inhibitors of Phosphoglycerate Dehydrogenase (PHGDH), Pharmaceuticals (Basel), 2020, 13(2):20.

2019

Aibidi Y, Guerrin C, Aleveque O, Leriche P, Delbaere S, Sanguinet L, Champagne B, BT-2-BOX: an assembly toward multi-modal and multi-level molecular system simple as a breeze, J Phys Chem C, 2019, 123, 11823-11832.

Berthet J, Agouridas L, Chen S, Allouchi H, Melnyk P, Champagne B, Delbaere S, Synthesis and Photoswitching properties of new derivatives of azoresveratrol, Dyes Pigment, 2019, 171, 107666.

Fernández B, Lara Ordóñez AJ, Fdez E, Mutez E, Comptdaer T, Leghay C, Kreisler A, Simonin C, Vandewynckel L, Defebvre L, Destée A, Bleuse S, Taymans JM, Chartier-Harlin MC, Hilfiker S, Centrosomal cohesion deficits as cellular biomarker in lymphoblastoid cell lines from LRRK2 Parkinson's disease patients, Biochemical J, 2019, 476(19), 2797-2813.

Graça VC, Calhelha RC, Nunes FM, Berthet J, Ferreira ICFR, Santos PF, Isolation of secondary metabolites from Geranium molle L. with anticancer potential, Ind Crops Prod, 2019, 142, 1-5.

Guerrin C, Aibidi Y, Sanguinet L, Leriche P, Aloise S, Orio M, Delbaere S, When light and acid play Tic-Tac-Toe with a nine-state molecular switch, J Am Chem Soc, 2019, 141, 19151-19160.

Hamdi I, Buntinx G, Poizat O, Delbaere S, Perrier A, Rikiya Y, Ken-ichi M, Takeshita M, Aloïse S, Unraveling Ultrafast Dynamics of the Photoswitchable Bridged Dithienylethenes Under Structural Constraints, Phys Chem Chem Phys, 2019, 21, 6407-6414.

Issa S, Prandina A, Bedel N, Rongved P, Yous S, Le Borgne M, Bouaziz Z, Carbazole scaffolds in cancer therapy: a review from 2012 to 2018, J Enzyme Inhib Med Chem, 2019, 34(1), 1321-1346.

Johansson LC, Stauch B, McCorvy JD, Han GW, Patel N, Huang XP, Batyuk A, Gati C, Slocum ST, Li C, Grandner JM, Hao S, Olsen RHJ, Tribo AR, Zaare S, Zhu L, Zatsepin NA, Weierstall U, Yous S, Stevens RC, Liu W, Roth BL, Katritch V, Cherezov V, XFEL structures of the human MT2 melatonin receptor reveal the basis of subtype selectivity, Nature, 2019, 569(7755), 289-292.

Liberelle M, Magnez R, Thuru X, Bencheikh Y, Ravez S, Quenon C, Drucbert AS, Foulon C, Melnyk P, Van Seuningen I, Lebegue N, MUC4-ErbB2 Oncogenic Complex: Binding studies using Microscale Thermophoresis and Surface Plasmon Resonance, Sci Rep, 2019, 9, 16678-85.

Rami M, Winum JY, Supuran C, Melnyk P, Yous S, (Hetero)aryl substituted thaizol-2,4-yl scaffold as human carbonic anhydrase I, II, VII and XIV activators, J Enzyme Inhib Med Chem, 2019, 34 (1), 224-229.

Sergeant N, Vingtdeux V, Eddarkaoui S, Gay M, Evrard C, Lefur N, Laurent C, Caillierez R, Obriot H, Larchanché PE, Farce A, Coevoet M, Carato P, Kouach M, Descat A, Dallemagne P, Buée-Scherrer V, Blum D, Hamdane M, Buée L, Melnyk P, New piperazine multi-action drugs prevent neurofibrillary degeneration and amyloid deposition, and preserve memory in animal models of Alzheimer’s disease. Neurobiol Disease, 2019, S0969-9961, 30327-9.

Sousa CM, Berthet J, Delbaere S, Coelho PJ, Enhancement of the color intensity of photochromic fused-naphthopyrans, Dyes Pigment, 2019, 169, 118-124.

Spillier Q, Vertommen D, Ravez S, Marteau R, Thémans Q, Corbet C, Feron O, Wouters J, Frédérick R, Anti-alcohol abuse drug disulfiram inhibits human PHGDH via disruption of its active tetrameric form through a specific cysteine oxidation, Sci Rep, 2019, 9(1), 4737.

Stauch B, Johansson LC, McCorvy JD, Patel N, Han GW, Huang XP, Gati C, Batyuk A, Slocum ST, Ishchenko A, Brehm W, White TA, Michaelian N, Madsen C, Zhu L, Grant TD, Grandner JM, Shiriaeva A, Olsen RHJ, Tribo AR, Yous S, Stevens RC, Weierstall U, Katritch V, Roth BL, Liu W, Cherezov V, Structural basis of ligand recognition at the human MT1 melatonin receptor, Nature, 2019, 569(7755), 284-288.

2018

Boot E, Butcher NJ, Udow S, Marras C, Mok KY, …., Mutez E, …, Bassett AS, International Research Group on 22q11.2DS-associated Parkinson's Disease. Typical features of Parkinson disease and diagnostic challenges with microdeletion 22q11.2, Neurology, 2018, 90(23), e2059-e2067.

Boulahjar R, Rincon Arias A, Bolteau R, Renault N, Coevoet M, Barczyk A, Duroux R, Yous S, Melnyk P, Agouridas L, Design and synthesis of 2,6-disubstituted-8-amino imidazo[1,2a]pyridines, a promising privileged structure, Bioorg Med Chem, 2018, 26, 3296-3307.

Cuvelier E, Méquinion M, Leghay C, Sibran W, Stievenard A, Sarchione A, Bonte MA, Vanbesien-Mailliot C, Viltart O, Saitoski K, Caron E, Labarthe A, Comptdaer T, Semaille P, Carrié H, Mutez E, Gressier B, Destée A, Chartier-Harlin MC, Belarbi K, Overexpression of Wild-Type Human Alpha-Synuclein Causes Metabolism Abnormalities in Thy1-aSYN Transgenic Mice, Front Mol Neurosci, 2018, 11, 321.

Duroux R, Agouridas L, Renault N, El Bakali J, Furman C, Melnyk P, Yous S, Antagonists of the aden osine A(2A) receptor based on a 2-arylbenzoxazole scaffold: Investigation of the C5-and C7-positions to enhance affinity, Eur J Med Chem, 2018, 144, 151-163.

Evrard C, Kieulen-Campard P, Coevoet M, Opsomer R, Tasiaux B, Melnyk P, Octave JN, Buée L, Sergeant N, Vingtdeux V, Contribution of the endosomal-lysosomal and proteosomal systems in amyloid-β precursor protein derived fragments processing, Front Cell Neurosci, 2018, 12, 435.

Gay M, Carato P, Coevoet M, Renault N, Larchanché PE, Barczyk A, Yous S, Buée L, Sergeant N, Melnyk P, New phenylaniline derivatives as modulators of amyloid protein precursor metabolism, Bioorg Med Chem, 2018, 26, 2151-64.

Gay M, Evrard C, Descamps F, Carato P, Renault N, Coevoet M, Eddarkaoui S, Baud C, Larchanché PE, Buée L, El Bakali J, Vingtdeux V, Sergeant N, Melnyk P, A Phenotypic Approach to the Discovery of Compounds that Promote Non-Amyloidogenic Processing of the Amyloid Precursor Protein: Toward a New Profile of Indirect β-Secretase Inhibitors, Eur J Med Chem, 2018, 159, 104-125.

Gibault F, Sturbaut M, Bailly F, Melnyk P, Cotelle P, Targeting Transcriptional Enhanced Associate Domains (TEADs), J Med Chem, 2018, 61(12), 5057-5072.

Gibault F, Coevoet M, Sturbaut M, Farce A, Renault N, Allemand F, Guichou JF, Drucbert AS, Foulon C, Magnez R, Thuru X, Corvaisier M, Huet G, Chavatte P, Melnyk P, Bailly F, Cotelle , Towards the Discovery of a Novel Class of YAP-TEAD Interaction Inhibitors by Virtual Screening Approach Targeting YAP-TEAD Protein-Protein Interface, Cancers, 2018, 10(5), 140. Invitation paper.

Guerrin C, Szalóki G, Berthet J, Sanguinet L, Orio M, Delbaere S, Indolino-oxazolidine Acido and Photochromic System investigated by NMR and DFT Calculations, J Org Chem, 2018, 82, 12028-12037.

Hamdi I, Buntinx G, Poizat O, Perrier A, Le Bras L, Delbaere S, Barrau S, Louati M, Takeshita M, Tokushige K, Takao M, Aloïse S, Excited-State Dynamics of Dithienylethenes Functionalized for Self-Supramolecular Assembly, J Phys Chem A, 2018, 122, 3572-3582.

Madero-Pérez J, Fdez E, Fernández B, Lara Ordóñez AJ, Blanca Ramírez M, Gómez-Suaga P, Waschbüsch D, Lobbestael E, Baekelandt V, Nairn AC, Ruiz-Martínez J, Aiastui A, López de Munain A, Lis P, Comptdaer T, Taymans JM, Chartier-Harlin MC, Beilina A, Gonnelli A, Cookson MR, Greggio E, Hilfiker S, Parkinson disease-associated mutations in LRRK2 cause centrosomal defects via Rab8a phosphorylation, Mol Neurodegener, 2018, 13, 3.

Mohamed SH, Quertinmont J, Delbaere S, Sanguinet L, Champagne B, Assessing the Structure of Octastate Molecular Switches Using H-1 NMR Density Functional Theory Calculations, J Phys Chem C, 2018, 122, 1800-1808.

Sousa CM, Berthet J, Delbaere S, Coelho PJ, Synthesis of Polycyclic Spironaphthofuran Derivatives by Acid-Catalyzed Domino Reaction of 2-Naphthols with Tetraarylbut-2-yne-1,4-diols, Eur J Org Chem, 2018, 3291-97.

Taymans JM, Chartier-Harlin MC, In silico and Wet Bench Interactomics Sheds Light on the Similitudes and Differences between Human ROCO Proteins, Proteomics, 2018, e1800103.

2017

Belarbi K, Cuvelier E, Destee A, Gressier B, Chartier-Harlin MC, NADPH oxidases in Parkinson's disease: a systematic review, Mol. Neurodegener, 2017, 12, 84.

Berdnikova DV, Aliyeu TM, Delbaere S, Fedorov YV, Jonusauskas G, Novikov VV, Pavlov AA, Peregudov AS, Shepel NE, Zubkov FI, Fedorova OA, Regio- and stereoselective [2+2] photocycloaddition in Ba2+ templated supramolecular dimers of styryl-derivatized aza-heterocycles, Dyes Pigment, 2017, 139, 397-402.

Civiero L, Cogo S, Kiekensl A, Morganti C, Tessari I, Lobbestael E, Baekelandt V, Taymans JM, Chartier-Harlin MC, Franchin C, Arrigoni G, Lewis PA, Piccoli G, Bubacco L, Cookson MR, Pinton P, Greggio E, PAK6 Phosphorylates 14-3-3 gamma to Regulate Steady State Phosphorylation of LRRK2, Front Molec Neurosci, 2017, 10, 417.

Donnier-Marechal M, Carato P, Larchanche PE, Ravez S, Boulahjar R, Barczyk A, Oxombre B, Vermersch P, Melnyk P , Synthesis and pharmacological evaluation of benzamide derivatives as potent and selective sigma-1 protein ligands, Eur J Med Chem, 2017, 138, 964-978.

Duroux R, Rami M, Landagaray E, Ettaoussi M, Caignard DH, Delagrange, Melnyk P, Yous S, Synthesis and biological evaluation of new naphtho- and quinolinocyclopentane derivatives as potent melatoninergic (MT1/MT2) and serotoninergic (5-HT2C) dual ligands, Eur J Med Chem, 2017, 141, 552-566.

Duroux R, Renault N, Cuelho JE, Agouridas L, Blum D, Lopes LV, Melnyk P, Yous S, Design, synthesis and evaluation of 2-aryl benzoxazoles as promising hit for the A2A receptor, J Enzyme Inhib Med Chem, 2017, 32, 850-864.

Duroux R, Ciancetta A, Mannes P, Yu JH, Boyapati S, Gizewski E, Yous S, Ciruela F, Auchampach JA, Gao ZG, Jacobson KA, Bitopic fluorescent antagonists of the A(2A) adenosine receptor based on pyrazolo[4,3-e][1,2,4]triazolo[1,5-c]pyrimidin-5-amine functionalized congeners, MedChemComm, 2017, 8, 1659-1667.

Edwards TC, Lomonosova E, Patel JA, Li Q, Villa JA, Gupta AK, Morrison LA, Bailly F, Cotelle P, Giannakopoulou E, Zoidis G, Tavis JE , Inhibition of hepatitis B virus replication by N-hydroxyisoquinolinediones and related polyoxygenated heterocycles, Antiviral Res, 2017, 143, 205-217.

Gibault F, Bailly F, Corvaisier M, Coevoet M, Huet G, Melnyk P, Cotelle P, Molecular Features of the YAP Inhibitor Verteporfin: Synthesis of Hexasubstituted Dipyrrins as Potential Inhibitors of YAP/TAZ, the Downstream Effectors of the Hippo Pathway, ChemMedChem, 2017, 12, 954-961.

Guérin J, Léaustic A, Berthet J, Métivier R, Guillot R, Delbaere S, Nakatani K, Yu P, Light-Controlled Release and Uptake of Zinc Ions in Solution by a Photochromic Terthiazole-Based Ligand, Chem Asian J, 2017, 12, 853-859.

Hensman Moss DJ, Pardiñas AF, Langbehn D, Lo K, Leavitt BR, Roos R, Durr A, Mead S, … Destee A, …..Simonin C, … Tabrizi SJ, Identification of genetic variants associated with Huntington's disease progression: a genome-wide association study, Lancet Neurol, 2017, 16, 701-711.

Landagaray E, Ettaoussi M, Rami M, Boutin JA, Caignard DH, Delagrange P, Melnyk P, Berthelot P, Yous S, New quinolinic derivatives as melatonergic ligands: Synthesis and pharmacological evaluation, Eur J Med Chem, 2017, 127, 621-631.

Méquinion M, Le Thuc O, Zgheib S, Alexandre D, Chartrel N, Rovère C, Hardouin P, Viltart O, Chauveau C, Long-Term Energy Deficit in Mice Causes Long-Lasting Hypothalamic Alterations after Recovery, Neuroendocrinology, 2017,105(4), 372-383.

Moors TE, Hoozemans JJ, Ingrassia A, Beccari T, Parnetti L, Chartier-Harlin MC, Viltart O, Vanbesien-Maillot CC, Therapeutic potential of autophagy-enhancing agents in Parkinson's disease, Mol Neurodegener, 2017,12, 11.

Nkiliza A, Chartier-Harlin MC, ATXN2 a culprit with multiple facets, Oncotarget, 2017, 8, 34028-29.

Pirat C, Dacquet C, Leclerc V, Hennuyer N, Beucher-Gaudin M, Zanirato G, Géant A, Staels B, Ktorza A, Farce A, Caignard DH, Berthelot P, Lebègue N, Anti-diabetic activity of fused PPAR gamma-SIRT1 ligands with limited body-weight gain by mimicking calorie restriction and decreasing SGK1 expression, Eur J Med Chem, 2017, 137, 310-326.

Ramirez MB, Lara Ordonez AJ, Fdez E, Madero-Perez J, Gonnelli A, Drouyer M, Chartier-Harlin MC, Taymans JM, Bubacco L, Greggio E, Hilfiker S, GTP binding regulates cellular localization of Parkinson's disease-associated LRRK2, Hum Mol Genet, 2017, 26, 2747-2767.

Rassu M, Del Giudice MG, Sanna S, Taymans JM, Morari M, Brugnoli A, Frassineti M, Masala A, Esposito S, Galioto M, Valle C, Carri MT, Biosa A, Greggio E, Crosio C, Iaccarino C, Role of LRRK2 in the regulation of dopamine receptor trafficking, PLoS One, 2017, 12, e0179082.

Ravez S, Corbet C, Spillier Q, Dutu AD, Mullarky E, Cantley LC, Feron O, Frédérick R, alpha-Ketothioamide Derivatives: A Promising Tool to Interrogate Phosphoglycerate Dehydrogenase (PHGDH), J Med Chem, 2017, 1591-1597.

Ravez S, Spillier Q, Marteau R, Feron O, Frédérick R, Challenges and Opportunities in the Development of Serine Synthetic Pathway Inhibitors for Cancer Therapy, J Med Chem, 2017, 1227-1237.

Sanguinet L, Berthet J, Szaloki G, Aleveque O, Pozzo JL, Delbaere S, 13 metastable states arising from a simple multifunctional unimolecular system, Dyes Pigment, 2017, 137, 490-498.

Sejwal K, Chami M, Rémigy H, Vancraenenbroeck R, Sibran W, Sütterlin R, Baumgartner P, McLeod R, Chartier-Harlin MC, Baekelandt V, Stahlberg H, Taymans JM, Cryo-EM analysis of homodimeric full-length LRRK2 and LRRK1 protein complexes, Sci Rep, 2017, 7, 8667.

Sousa CM, Berthet J, Delbaere S, Polonia A, Coelho PJ, Control of the Switching Speed of Photochromic Naphthopyrans through Restriction of Double Bond Isomerization, J Org Chem, 2017, 82, 12028-12037.

Sousa CM, Berthet J, Delbaere S, Coelho PJ, A closer look at the photochromism of vinylidene-naphthofurans, Dyes Pigment, 2017, 137, 593-600.

Stievenard A, Méquinion M, Andrews ZB, Destée A, Chartier-Harlin MC, Viltart O, Vanbesien-Maillot CC, Is there a role for ghrelin in central dopaminergic systems? Focus on nigrostriatal and mesocorticolimbic pathways, Neurosci Biobehav Rev, 2017, 73, 255-275.

Taymans JM, Regulation of LRRK2 by Phosphatases, Adv Neurobiol, 2017, 14, 145-160.

Taymans JM, Mutez E, Drouyer M, Sibran W, Chartier-Harlin MC, LRRK2 detection in human biofluids: potential use as a Parkinson's disease biomarker?, Biochem Soc Trans, 2017, 45, 207-212.

Verny C, Bachoud-Lévi AC, Durr A, Goizet C, Azulay JP, Simonin C, Tranchant C, Calvas F, Krystkowiak P, Charles P, Youssov K, Scherer C, Prundean A, Olivier A, Reynier P, Saudou F, Maison P, Allain P, von Studnitz E, Bonneau D; CYST-HD Study Group, A Randomized, Double-Blind, Placebo-Controlled Trial Evaluating Cysteamine in Huntington's Disease, Mov Disord, 2017, 32, 932-936.

Patents

Patents deposited

  • Melnyk P, Carato P, Burlet S, Nguyen TH, Verwaerde P, Sergeant N, Estrella C. γ-carbolines derivatives for the treatment of neurodegenerative diseases, EP 13305927.9
  • Melnyk P, Carato P, Burlet S, Nguyen TH, Verwaerde P, Sergeant N, Estrella C. β-carbolines derivatives for the treatment of neurodegenerative diseases, EP 13305928.7
  • Carato P, Descamps F, El Bakali J, Evrard C, Gay M, Melnyk P, Renault N, Sergeant N, Vingtdeux V. Polyamino biaryl compounds and their use. EP 18305932.8

Accepted Patents

  • Melnyk P, Carato P, Burlet S, Nguyen TH, Verwaerde P, Sergeant N, Estrella C. Beta and gamma-carbolines derivatives for the treatment of neurodegenerative diseases, PCT/EP2014/063771. WO2014/207240. PCT/EP2015/063370
  • Melnyk P, Carato P, Burlet S, Nguyen TH, Verwaerde P, Sergeant N, Estrella C. Na-substituted carbolines derivatives for the treatment of neurodegenerative diseases, EP 13305929.5, PCT/EP2014/063772, WO2014/207241
  • Melnyk P, Vermersch P, Carato P, Vanteghem-Oxombre B, Zephir H, Donnier-Maréchal M. Compounds, pharmaceutical composition and their use in treating neurodegenerative diseases, EP14305919.4, PCT/EP2015/063370. Licence en discussion
  • Tavis JE, Cotelle P, Bailly F. N-Hydroxyisoquinolindione inhibitors of HBV replication. PCT/US2017/022738

Licensed patents

  • Melnyk P, Sergeant N, Buée L, Delacourte A. Use of 1,4-bis(3-aminoalkylyl)piperazine derivatives in the treatment of neurodegenerative diseases, WO 2006 051489, PCT/IB2005/053676
    Licence exclusive accordée à AlzProtect dans le domaine des maladies neurodégénératives.
    Molécule actuellement en phase 2 chez l’homme.
  • Barrier M, Buée L, Burlet S, Delacourte A, Estrella C, Melnyk P, Sergeant N, Verwaerde P. Sulfate salts of N-(3-(4-(3-(diisobutylamino)propyl)piperazin-1-yl)propyl)-1H-benzo[d]imidazol-2-amine, preparation thereof and use of the same. WO2014/102339.
    Licence exclusive accordée à AlzProtect dans le domaine des maladies neurodégénératives.
    Molécule actuellement en phase 2 chez l’homme.
  • Melnyk P, Le Fur N, Gay M, Sergeant N, Buée L. Novel 1,4-bis(3-aminopropyl)piperazine derivative and its use . EP 15305384.8. PCT/EP2016/055633. Licence exclusive accordée à AlzProtect dans le domaine des maladies neurodégénératives.

PhD thesis

PhD in progress

  • Antoine MARCHAND (4th year) under the supervision of Dr JM Taymans
    "LRRK2 and vesicular trafficking deficits in Parkinson's disease"
  • Alessia Sarchione (4th year) under the supervision of Dr MC Chartier-Harlin
    "Defects in membrane trafficking in Parkinson's disease"
  • Florine TOULOTTE (3rd year) under the supervision of Pr P Cotelle
    "Synthesis and design of selective modulators of the YAP (TAZ) -TEAD interaction"
  • Andriana FIGUEROA-GARCIA (3rd year) under the supervision of Dr MC Chartier-Harlin
    "Targeting translation during alpha-synuclein overexpression in Parkinson's disease"
  • Liesel Mary GOVEAS (3rd year) under the supervision of Dr JM Taymans
    "Targeting of the kinase of Parkinson's disease “Leucine Rich repeat kinase 2” (LRRK2)"
  • Pasquale SILEO (3rd year) under the supervision of Pr P Cotelle
    "Study of the Hippo pathway in Huntington's disease"
  • Nicolas STOUP (3rd year) under the co-supervision of Dr I Van Seuningen / Pr N Lebègue
    " The MUC4-ErbB2 complex: from the structure-function relationship towards therapeutic targeting"
  • Alexandre GOBERT (2nd year) under the supervision of Pr N Lebègue
    " Design, synthesis and evaluation of new activators of SIRT1 in neurodegenerative diseases"
  • Amélie (1st year) under the supervision of Dr S Yous
    "Design, synthesis and evaluation of potential A2A receptor antagonists and dual ligands targeting A2A / mGlu5 receptors in the treatment of neurodegenerative diseases"
  • Justine (1st year) under the supervision of Pr N Lebègue
    "Design, synthesis and pharmacological evaluation of new antimalarial compounds"

Defended PhD since 2017

  • Marie TAUTOU (defended the 29/10/2021)
    « Mise en évidence du mode d'action de molécules anti-Alzheimer et recherche de leur cible ». Co-supervision of Dr N Sergeant / Pr P Melnyk
  • Raphael BOLTEAU (defended the 02/10/2020)
    « Conception, synthèse et évaluation pharmacologique d’antagonistes des récepteurs A2A et de ligands duaux ciblant les récepteurs A2A et mGlu5». Supervision of Dr S Yous
  • Maxime LIBERELLE (defended the 10/10/2019)
    « Focus on the protein-protein interface of MUC4 / ErbB2 complex : a structural approach». Supervision of Pr N Lebègue
  • Florian DESCAMPS (defended the 03/10/2019)
    « Conception, Synthèse et Evaluation de molécules interagissant avec la protéine VCP pour le traitement de maladies neurodégénératives». Supervision of Pr P Melnyk
  • Manon STURBAUT (defended the 27/09/2019)
    « Conception, Synthèse et Evaluation d’inhibiteurs du complexe protéique YAP-TEAD». Supervision of Pr P Cotelle
  • Mathieu DROUYER (defended the 20/12/2018)
    « Ciblage de la kinase parkinsonnienne LRRK2». Supervision of Dr JM Taymans
  • Clément GUERRIN (defended the 28/09/2018)
    « Etude des propriétés de photocommutation de composés photoactivables couplée à une irradiation in situ et par calculs TD-DFT». Supervision of Pr S Delbaere (LASIR)
  • Floriane GIBAULT (defended the 13/10/2017)
    « Conception, Synthèse et Evaluation d’inhibiteurs du complexe protéique YAP-TEAD». Supervision of Pr P Cotelle
  • Romain DUROUX (defended the 22/09/2017)
    « Conception, Synthèse et Evaluation d’antagonistes des récepteurs A2A». Supervision of Dr S Yous
  • Elodie CUVELIER (defended in 2017)
    « Modulation pharmacologique de la glucocérébrosidase chez un modèle murin de syndrome parkinsonien surexprimant l’alpha-synucléine». Supervision of Dr K Belarbi