[en] Tackling thrombotic disorders without affecting the hemostatic capacity remains a challenge in medicine. One of the strategies in the search for safer antithrombotic therapies is to target coagulation factor XIIa (FXIIa).[1] This strategy have two substantial advantages :
1. No bleeding risk
2. Additional anti-inflammatory effects
After limited results with the traditional medicinal chemistry approach (inhibitors in the μM range) [2], we decided to apply fragment-based drug discovery approach (FBDD). In its first step, FBDD strongly depends on the ability to detect and gauge weak affinity binders. In the scope of validating the fragment hits, the most robust strategy is to apply orthogonal techniques.
In this work, we investigate the suitability of microscale thermophoresis and capillary electrophoresis for the discovery of new fragments that bind FXIIa.
[1] a) J.I.Weitz, Thromb Res, 141 Suppl 2 (2016) S40-45; b) J.C. Fredenburgh, P.L. Gross, J.I. Weitz, Blood, 129 (2017) 147-154; c) A.T. Long, E. Kenne, R. Jung, T.A. Fuchs, T. Renne, J Thromb Haemost, 14 (2016) 427-437.
[2] a) S. Robert, C. Bertolla, B. Masereel, J.M. Dogné, L. Pochet, Journal of Medicinal Chemistry, 51 (2008) 3077-3080; b) C. Bouckaert, S. Serra, G. Rondelet, E. Dolušić, J. Wouters, J.M. Dogné, R. Frédérick, L. Pochet, Eur J of Med Chem, 110 (2016) 181-194
Research Center/Unit :
CIRM - Centre Interdisciplinaire de Recherche sur le Médicament - ULiège NAmur Research Institute for Life - NARILIS
Disciplines :
Pharmacy, pharmacology & toxicology Chemistry
Author, co-author :
Davoine, Clara ; Université de Liège - ULiège / Université de Namur - UNamur > Département de pharmacie > Analyse des médicaments / Namur Medicine & Drug Innovation Center (NAMEDIC – NARILIS) > Doct. sc. bioméd. & pharma. (paysage)
Farcas, Elena ; Université de Liège - ULiège > Département de pharmacie > Analyse des médicaments
Thabault, Léopold; Université Catholique de Louvain - UCL > Louvain Drug Research Institute (LDRI)
Simon, François; Université de Namur - UNamur > Département de chimie > Chimie Organique de Synthèse (COS)
Bouckaert, Charlotte; Université de Namur - UNamur > Département de pharmacie > Namur Medicine & Drug Innovation Center (NAMEDIC – NARILIS)
Frédérick, Raphaël; Université Catholique de Louvain - UCL > Louvain Drug Research Institute (LDRI)
Lanners, Steve; Université de Namur - UNamur > Département de chimie > Chimie Organique de Synthèse
Pochet, Lionel; Université de Namur - UNamur > Département de pharmacie > Namur Medicine & Drug Innovation Center (NAMEDIC – NARILIS)
Fillet, Marianne ; Université de Liège - ULiège > Département de pharmacie > Analyse des médicaments
Language :
English
Title :
Capillary electrophoresis and microscale thermophoresis in fragment-based drug discovery : development of screening bioassays towards FXIIa
Publication date :
24 March 2019
Event name :
7th RSC-BMCS Fragment-based Drug Discovery meeting (Fragment 2019)
Event organizer :
RSC BMCS
Event place :
Cambridge, United Kingdom
Event date :
du 24 mars 2019 au 26 mars 2019
Audience :
International
Peer reviewed :
Peer reviewed
Name of the research project :
Development of new compounds targeting coagulation factor XIIa using innovative microfluidic assays in the context of fragment-based drug discovery
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