References of "Hanson, Julien"
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See detailIdentification of modulators for SUCNR1 by screening of a SOSA library with a bioluminescent cAMP assay
Gilissen, Julie; Dupuis, Nadine ULg; Derj, Anouar et al

Conference (2014, November 21)

Background Succinic acid (SA), a metabolic component that takes part in the citric acid cycle, has been described as the cognate agonist for the orphan receptor SUCNR1 (GPR91). This receptor belongs to ... [more ▼]

Background Succinic acid (SA), a metabolic component that takes part in the citric acid cycle, has been described as the cognate agonist for the orphan receptor SUCNR1 (GPR91). This receptor belongs to the G Protein-Coupled Receptor family (GPCR), that play an essential role in regulating many physiological functions and represent 30% of targets for currently marketed drugs. Several studies on KO models suggested different roles for SUCNR1 through its inactivation. Nevertheless, the characterization of the pharmacology and physiology of SUCNR1 is limited by the lack of small molecules used as pharmacological tools. Methods In order to identify ligands modulating SUCNR1 Gαi activity, we adapted a specific cAMP assay based on a modified luciferase fused with cAMP binding domain (Glosensor® promega corporation). Upon cAMP binding, conformational changes induce luminescent signal. This sensitive assay was carried out in a real time measurements fashion. It was compatible with the screening of chemical libraries. We utilized a SOSA library based on the principle that active compounds might have an activity on new targets at high concentration. Results We performed a primary agonist screening on 1280 compounds of a SOSA library at two different concentrations (100 and 10µM) with a cAMP assay (Z’=0,4-0,6). We selected 114 out of them that were characterized at least by an increase (or decrease) of 20% of the luminescent signal from HEK293.SUCNR1 cells. These compounds were subjected to a secondary screening performed in triplicates. Results analysis provided 16 putative modulators of SUCNR1 Gαi activity. We followed a similar strategy in another screening to find candidates with an antagonist profile. In parallel, we docked a part of the ZINC database ‘‘lead-like’’ molecules against SUCNR1 protein built by homology modelling from the β2-adrenergic receptor. This virtual screening has sorted 30 compounds with substantial theoretical affinity. They are currently undergoing functional evaluation in the cAMP assay. Conclusions We set up a real-time luminometric cAMP assay for SUCNR1. We selected a dozen of putative modulators of SUCNR1 that were selected for thorough evaluation. Furthermore, we obtained 30 potentially active compounds from a virtual screening that are assayed for functional activity at the receptor. The pharmacology of hits is currently characterized with different models and assays. [less ▲]

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See detailIdentification, Design and Evaluation of Pharmacological tools for the orphan GPCR GPR22
Geubelle, Pierre ULg; Gilissen, Julie ULg; Dupuis, Nadine ULg et al

Poster (2014, November 21)

GPCRs are the largest family of membrane receptors and are characterized by seven transmembrane domains. This family of receptors is currently the most successfully targeted protein for therapeutic ... [more ▼]

GPCRs are the largest family of membrane receptors and are characterized by seven transmembrane domains. This family of receptors is currently the most successfully targeted protein for therapeutic purposes. GPR22 is a GPCR that was discovered in 1997. It has no known endogenous ligand and is thus considered "orphan". Its presence situated at the heart and brain levels makes it a potential target for new therapeutic pathways. The only information about its signaling channel could be its coupling with G proteins. This study consist in the identification of a synthetic ligand of GPR22 receptor to use it as a pharmacological tool in the study of the signaling channels of GPR22 in order to understand its role and to validate it as a new therapeutic target. The initial hypothesis was that GPR22 is coupled to the Gαi protein. [less ▲]

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See detailLigand-independent Identification of orphan GPCR Signaling pathways
Dupuis, Nadine ULg; Gilissen, Julie; Derj, Anouar ULg et al

Conference (2014, July 16)

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See detailLIGAND-INDEPENDENT IDENTIFICATION OF ORPHAN GPCR ARRESTIN BINDING
Dupuis, Nadine ULg; Gilissen, Julie ULg; Derj, Anouar ULg et al

Poster (2014, June 05)

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See detailIdentification of chemical probes and signaling pathways for the orphan GPCR GPR27
Dupuis, Nadine ULg; Gilissen, Julie ULg; Pirotte, Bernard ULg et al

Poster (2013, June 06)

The largest family of membrane receptors is represented by G protein-coupled receptors (GPCRs), which are characterized by 7 transmembrane domains. Even if marketed drugs currently target only 10% of all ... [more ▼]

The largest family of membrane receptors is represented by G protein-coupled receptors (GPCRs), which are characterized by 7 transmembrane domains. Even if marketed drugs currently target only 10% of all GPCRs, they represent more than 30% of all small molecules based therapies. The physiological and pathophysiological role of a GPCR is defined by its expression pattern, signaling pathway and specific ligand[1]. GPCRs which have not yet been associated to a physiological ligand are called orphan GPCRs and represent ~100 of the ~370 human non-odorant GPCRs[2]. This project aims at identifying and developing pharmacological tools for GPR27 (SREB1), one of these orphan receptors. GPR27 has recently been shown to have a role in the regulation of insulin promoter activity and insulin secretion[3]. Nevertheless, the pharmacology of GPR27 remains elusive and the lack of appropriate pharmacological tools dramatically restricts the understanding of its function and its validation as a drug target. Thus, we plan to study its signaling pathway and to develop screening methods that will allow us to identify small molecules able to interact with GPR27. These are important steps toward understanding its function and evaluating GPR27 as a potential drug target, for instance in insulin-related metabolic disorders such as type II diabetes or in other pathologies where it might be involved. References 1) Wise, A., et al. (2002). Drug discovery today, 7, 235 2) Fredriksson, R., et al. (2003). Molecular pharmacology, 63, 1256 3) Ku, G. M., et al. (2012). PLoS genetics, 8, e1002449 [less ▲]

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See detailSynthesis and pharmacological evaluation of 2-aryloxy/arylamino-5-cyanobenzenesulfonylureas as novel thromboxane A2 receptor antagonists
Bambi-Nyanguile, Sylvie-Mireille; Hanson, Julien ULg; OOMS, Annie ULg et al

in European Journal of Medicinal Chemistry (2013), 65C

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See detailChemical probes and signaling pathways for the orphan GPCR GPR27
Dupuis, Nadine ULg; Gilissen, Julie ULg; Pirotte, Bernard ULg et al

Poster (2013, January 28)

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See detailHeterologously expressed formyl peptide receptor 2 (FPR2/ALX) does not respond to lipoxin A4
Hanson, Julien ULg; Ferreiros, Nerea; Pirotte, Bernard ULg et al

in Biochemical Pharmacology (2013), 85

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See detailDevelopment of original 2-aryloxy/arylamino-5-cyanobenzenesulfonylureas as thromboxane A2 receptor antagonists
Bambi Nyanguile, Sylvie-Mireille ULg; Hanson, Julien ULg; Dogné, Jean-Michel et al

Poster (2012, August)

A series of novel 2-aryloxy/arylamino-5-cyanobenzenesulfonylureas were synthesized. The newly synthesized compounds were tested in vitro and ex vivo as thromboxane A2 receptor antagonists. Some of the ... [more ▼]

A series of novel 2-aryloxy/arylamino-5-cyanobenzenesulfonylureas were synthesized. The newly synthesized compounds were tested in vitro and ex vivo as thromboxane A2 receptor antagonists. Some of the test compounds showed potent thromboxane A2 receptor antagonist activity. Three compounds (7h, 8h and 8e) were identified as leads for further pharmacological and toxicological studies. [less ▲]

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See detailRole of HCA₂ (GPR109A) in nicotinic acid and fumaric acid ester-induced effects on the skin
Hanson, Julien ULg; Gille, Andreas; Offermanns, Stefan

in Pharmacology & Therapeutics (2012)

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