M2SV : Drugs and Molecules for Living Systems
UMR 1177 M2SV – Lille University – INSERM – Institut Pasteur de Lille
The laboratory’s mission is to design and synthesize drug candidates with an innovative mode of action, aimed at achieving clear therapeutic progress in indications where the medical need is poorly satisfied. This interdisciplinary molecular invention work is inspired by the most recent discoveries made on infectious diseases, metabolic diseases and cancer. By discovering molecules, new therapeutic solutions can be offered and the involvement of the mechanisms highlighted by biologists in the pathophysiological processes can be validated. The design and optimisation of new drugs require interdisciplinary expertise covering chemistry, physics, biology and in silico modelling. Indeed, the active ingredient of modern drugs, whether they are synthetic or biological in origin, is always defined at the molecular, or even the atomic, level. This particular molecular structure – perfected by the researchers of the unit – is the key to all the properties of the drug. It conditions its ability to cross the physical and chemical barriers between the different biophases (intestine, blood, tissues, brain, etc.) of the body, and to attain the set target. It is also key to its interaction with the intended target and the achievement of the desired effect. Beyond the therapeutic goal, molecules also serve as valuable tools that help biologists better understand how the cell and living organisms work and verify that the proposed targets for treating diseases are relevant. Researchers are working on antimicrobial resistance (AMR), viral infections (COVID-19), type 2 diabetes and NASH, certain forms of cancer and autoimmune diseases.
The Strategic Steering Committee of the laboratory is composed of the tenured researchers and is headed by Benoit Deprez.
- TB-Boost project : drug candidate BVL-GSK098 has entered Phase 1 clinical trials.
From a collaboration, established in 2011 between our team, the group of A. Baulard and Bioversys, to develop ethionamide boosters for the treatment of tuberculosis, we identified and optimized powerful compounds capable of overcoming resistance to Ethionamide on multi-resistant strains. This scientific breakthrough, published in Science in March 2017, resulted in the signing of a contract with GSK for the preclinical and clinical development of this chemical series. The entry into the clinical phase of the drug candidate BVL-GSK098 was achieved in December 2020 with administration to the first healthy volunteer. The phase 2A study is scheduled for mid-2021.
- European CAPSTONE project granted
Our research team has been awarded a European project H2020-Marie-Curie European Training Network (call 2020- grant agreement No 954992) for the period 2021-2024. Pr Deprez-Poulain is the coordinator of this consortium composed of 10 beneficiaries, 9 partner organizations and including 7 industrials. This multidisciplinary project aims to train experts in structural biology, immunology, biochemistry, proteomics and medicinal chemistry to develop small molecules to treat autoimmune diseases and cancer, based on the modulation of endoplasmic reticulum aminopeptidases (ERAP). The 15 PhD students will be recruited in 2021.
- COVID-19 projects :
Our research team and U1019 unit have jointly initiated, as early as February 2020, a research work to identify antiviral compounds effective against SARS-CoV-2, the etiologic agent of COVID-19. Two approaches have been employed. The first aims to propose a drug for the clinic in less than 12 months through repositioning. The second, longer-term strategy aims to design a novel molecule specifically to inhibit SARS-CoV-2 and all related coronaviruses.
Research Group : Drugs and Molecules for treating viral infections :
Research Group : Drugs and Molecules for treating metabolic diseases, autoimmune diseases and cancer :
Inhibitors of Insulin Degrading Enzyme in metabolic diseases Region-FEDER CPER grant, ANR BETASTRESS, EGID/PRECIDIAB
U1177 : R. Deprez-Poulain (PI) ; Collaboration with Dr N. Hennuyer (U1011), Pr S. Lancel (U1167), Pr P. van Endert (INEM), Pr M. Solimena (IPI Helmholz Munchen, GE), Pr W.-J. Tang (U. Chicago).
Inhibitors of aminopeptidases of the endoplasmic reticulum for the treatment of autoimmune diseases and cancer FRM ERAP4DIAB, ANR ERAPIMM & H2020 MSCA ETN CAPSTONE consortium
U1177 : R. Deprez-Poulain (PI) ; Collaboration with Pr P. van Endert (INEM), Pr D. Launay (INFINITE-U1286), Dr. E. Stratikos (NSCRD), CAPSTONE consortium.
Research Group : Drugs and Molecules for fighting multidrug-resistant bacteria (Anti-infectious Drug Discovery (AIDD)) :
U1177 : N. Willand (PI) ; Collaboration : U1019 CIIL : https://era4tb.org/
Professor, unit director
ORCID number : 0000-0002-2777-4538
ORCID number : 0000-0001-7920-3430
ORCID number : 0000-0003-0554-873X
ORCID number : 0000-0002-3835-4619
ORCID number : 0000-0001-6895-276X
ORCID number : 0000-0002-6076-2934
Nour BOU KARROUM
Chau Phi DINH
ORCID number : 0000-0002-0784-0462
ORCID number : 0000-0003-2863-5721
ORCID number : 0000-0002-8416-5253
Assistant engineer – Safety and risk prevention assistant
Hoguet V., Lasalle M., Maingot M., Dequirez G., Boulahjar R., Leroux F., Piveteau C., Herledan A., Biela A., Dumont J., Chávez-Talavera O., Belloy L., Duplan I., Hennuyer N., Butruille L., Lestavel S., Sevin E., Culot M., Gosselet F., Staels B., Deprez B., Tailleux A., Charton J.
Beyond the Rule of 5: Impact of PEGylation with Various Polymer Sizes on Pharmacokinetic Properties, Structure–Properties Relationships of mPEGylated Small Agonists of TGR5 Receptor.
Journal of Medicinal Chemistry, 2021, in press.
Bosc, D., Camberlein, V., Gealageas, R., Castillo-Aguilera, O., Deprez, B., & Deprez-Poulain, R.
Kinetic Target-Guided Synthesis: reaching the age of maturity.
J. Med. Chem.,2020, 63(8): 3817–3833; 10.1021/acs.jmedchem.9b01183.
Montaigne, D., Marechal, X., Modine, T., Coisne, A., Mouton, S., Fayad, G., Ninni, S., Klein, C., Ortmans, S., Seunes, C., Potelle, C., Berthier, A., Gheeraert, C., Piveteau, C., Deprez-Poulain, R., Eeckhoute, J., Duez, H., Lacroix, D., Deprez, B., Jegou, B., Koussa, M., Edme, J. L., Lefebvre, P., & Staels, B.
Daytime variation of perioperative myocardial injury in cardiac surgery and its prevention by Rev-Erbalpha antagonism: a single-centre propensity-matched cohort study and a randomised study.
The Lancet,2018, 391(10115): 59–69.10.1016/s0140-6736(17)32132-3.
Guieu, B ; Jourdan, JP ; Dreneau, A ; Willand, N ; Rochais, C ; Dallemagne, P.
Desirable drug-drug interactions or when a matter of concern becomes a renewed therapeutic strategy.
Drug Discov Today, 2020, article in press. 10.1016/j.drudis.2020.11.026.
Faïon L., Djaout K., Frita R., Pintiala C., Cantrelle F. X., Moune M., Vandeputte A., Bourbiaux K., Piveteau C., Herledan A., Biela A., Leroux F., Kremer L., Blaise M., Tanina A., Wintjens R., Hanoulle X., Déprez B., Willand N., Baulard A. R., Flipo M.
Discovery of the first Mycobacterium tuberculosis MabA (FabG1) inhibitors through a fragment-based screening.
Eur J Med Chem, 2020, vol 200, p112440. 10.1016/j.ejmech.2020.112440.
Drugs ; Metalloprotease ; CAPSTONE-ETN ; Inhibitors ; KTGS ; ERAP ; IDE ; Macrocycles ; Chemical probes ; Antibiotics ; Anti-infective agents ; Transcription factors ; Chemical biology ; Medicinal chemistry ; Privileged structures ; AMR ; COVID-19 : SARS-CoV-2 ; Antiviral
Professor at Lille University
03 20 96 40 24