Scientific topics
Keywords
ITMO
Last update 2020-10-16 09:16:46.332
Rebecca Deprez-Poulain Rebecca Deprez-Poulain, Pr, PhD, PharmD
Course and current status
French and foreign degrees
- Bachelor of Science in chemistry at Juniata College (PA, USA), 1995.
- Master in organic chemistry at USTL (Lille, FR) 1996 (DEA)
- Engineer Degree in chemistry at HEI (Lille, FR) 1996.
- PhD in organic chemistry at USTL with honors (Lille, FR), 1999.
- Degree in Drug Design at the University of Lille 2 (ICPAL, Lille) 2001.
- Habilitation for research supervision (HDR) at the University of Lille 2, 2004.
- PharmD at the University of Lille 2, 2009
Prizes and Honors
- Member of the Institut Universitaire de France 2015 promotion
- Research Incentive Prize “Prix d'Encouragement à la Recherche” 2009 – Société de Chimie Thérapeutique (SCT)-Servier (French Medicinal Chemistry Society)
Research & Professional experiences
2010-now: Full Professor in Medicinal Chemistry - School of Pharmacy, Lille, France.
- Team leader @ Inserm U1177 Institut Pasteur de Lille, University of Lille: www.deprezlab.fr
- Metalloprotease inhibitors in metabolic, autoimmune diseases and cancer
2002-2010: Ass. Professor- School of Pharmacy, Lille, France.
- Team leader @ CNRS UMR8525 then INSERM U1177 (formerly U761) Institut Pasteur de Lille (FR) University of Lille:www.deprezlab.fr
- Metalloprotease inhibitors in infectious metabolic diseases, osteoarthritis and Alzheimer’s disease
2001-2002: PostDoc fellow (ATER)- School of Pharmacy, Lille, France.
- Researcher @ CNRS UMR8525 Lille (FR)
- Antimalarial PfAM1 inhibitors
1999-2001: PostDoc fellow, School of Pharmacy, University of Lille2 (FR).
- Researcher @ CNRS UMR8525 Lille (FR)
- Design of heterocyclic libraries for screening on C. elegans. (coll. DeVGen.NV, Ghent, BE).
1996-1999: PhD student at CEREP.SA (Campus Pasteur, Lille, France).
- Supervisors Pr Tartar/Pr Sergheraert
- Combinatorial chemistry for the discovery & optimization of leads, application to the mu opiate receptor.
Scientific summary
Coordinator of the H2020 MSCA-ITN CAPSTONE (www.capstone-etn.eu)
My current scientific activity focuses on the modulation of metalloproteases using small chemical compounds.
- Since 2007, my team developed a targeted library of zinc-binding compounds that allowed exploring the several metalloprotease families. Therapeutic applications of inhibitors of such enzymes include infectious, immune and metabolic diseases. In the M1 family, we discovered the first drug-like inhibitors of the plasmodial aminopeptidase PfAM1 a malarial protease (J. Med. Chem 2007 & 2012) and original neutral aminopeptidase APN inhibitors (Bioorg. Med Chem 2007). In the M12 family, we focussed on aggrecanases inhibitors (Fut. Med. Chem. 2014, Eur J Med Chem 2013, Bioorg Med Chem Lett 2010). For neprilysin (M13 family) we designed new inhibitors (MedChemComm 2012) using solid phase synthesis on lanterns.
- In the past years, we have been studying Insulin Degrading Enzyme (IDE, M16 family) to decipher its complex role in Type-2 diabetes and Alzheimer’s disease thanks to pharmacological chemical probes. We disclosed the first exosite binders (Eur JMedChem 2014 & 2015), the first cell-penetrant, in vivo active IDE inhibitor using an original KTGS based on hydroxamic acids, and demonstrated that acute IDE inhibition induced a paradoxical glucose intolerance, in line with the phenotype of the IDE-KO animals (Nature Comm 2015, Elife 2018). We also showed that Ebselen is the most potent inhibitor of IDE (Eur JMedChem 2019). We are also interested in the Aminopeptidases of the ER (ERAP, M1 family) inhibitors (ACS Med Chem Lett 2017).
- For our projects targeting metalloproteases we developed an expertise in hydroxamic acids (and other zing binding groups), in Kinetic Target guided synthesis (Nature Comm 2015, Fut. Med. Chem. 2016, J Med Chem 2020) and in tools to measure biological stability of chemical compounds (JMedChem 2017, Lancet 2018) and target engagement using CETSA (SLASDiscov 2020). In particular for hydroxamic acids, we designed the first medchem toolbox to optimize their plasma stability (JMedChem 2009 & 2017)
- Also we developed several chemical methodologies to access bioactive compounds, heterocycles and original nature-inspired compounds. We disclosed the original synthesis of oxadiazoles (Tet lett 2001, Nature Med 2009), solvent-free microwave irradiation to access bicyclic lactams (Green Chem 2010,2012), polymer-supported chemistries (BMCL 2009, Eur J Med Chem 2011, MedChemComm 2012), use of T3P (Tet Lett 2012), or water-based synthesis (TetLett 2013).
