Ngo, Tony and Kufareva, Irina and Coleman, James L J and Graham, Robert M and Abagyan, Ruben and Smith, Nicola J (2016) Identifying ligands at orphan GPCRs: current status using structure-based approaches. British Journal of Pharmacology, 173 (20). pp.2934-2951. ISSN 1476-5381 (OA)
Full text not available from this repository.Abstract
G protein-coupled receptors (GPCRs) are the most successful pharmaceutical targets in history. Nevertheless, the pharmacology of many GPCRs remains inaccessible as their endogenous or exogenous modulators have not been discovered. Tools that explore the physiological functions and pharmacological potential of these 'orphan' GPCRs, whether they be endogenous and/or surrogate ligands, are therefore of paramount importance. Rates of receptor deorphanisation by traditional reverse pharmacology efforts have slowed, mandating the development of more sophisticated and efficient ligand screening approaches. Here we discuss the use of structure-based ligand discovery approaches to identify small molecule modulators for exploring the function of orphan GPCRs. Such efforts have been buoyed by the growing number of GPCR crystal structures solved in the past decade, providing a broad range of template structures for homology modelling of orphans. This review discusses approaches to establishing the appropriate signalling assays to test orphan receptor activity and provides current examples of structure-based methods for orphan GPCR ligand identification.
| Item Type: | Article |
|---|---|
| Additional Information: | Article available for free from publisher's website |
| Subjects: | R Medicine > R Medicine (General) |
| Depositing User: | Repository Administrator |
| Date Deposited: | 14 Mar 2016 00:42 |
| Last Modified: | 08 Mar 2017 02:58 |
| URI: | https://eprints.victorchang.edu.au/id/eprint/395 |
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