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Curr Opin Cell Biol. 2014 Apr;27:117-25. doi: 10.1016/j.ceb.2013.12.002. Epub 2013 Dec 31.

Employing novel animal models in the design of clinically efficacious GPCR ligands.

Author information

1
MRC Toxicology Unit, University of Leicester, Hodgkin Building, Leicester LE1 9HN, UK.
2
MRC Toxicology Unit, University of Leicester, Hodgkin Building, Leicester LE1 9HN, UK. Electronic address: tba@le.ac.uk.

Abstract

The headline success of targeting GPCRs in human diseases has masked the fact that many GPCR drug discovery programmes fail. This is despite a substantial increase in our understanding of GPCR pharmacology that has provided an array of ligands that target both orthosteric and allosteric sites as well as ligands that show stimulus bias. From this plethora of pharmacological possibilities, can we design ligand properties that would deliver maximal clinical efficacy with lowest toxicity? This may be achieved through animal models that both validate a particular GPCR as a target as well as revealing the signalling mechanisms that underlie receptor-mediated physiological and clinical responses. In this article, we examine recent novel transgenic models being employed to address this issue.

PMID:
24680437
PMCID:
PMC3989050
DOI:
10.1016/j.ceb.2013.12.002
[Indexed for MEDLINE]
Free PMC Article

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