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Abstract :
[en] 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
