Journal
CURRENT OPINION IN CELL BIOLOGY
Volume 27, Issue -, Pages 117-125Publisher
CURRENT BIOLOGY LTD
DOI: 10.1016/j.ceb.2013.12.002
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Funding
- MRC [MC_UP_A600_1110] Funding Source: UKRI
- Biotechnology and Biological Sciences Research Council [1653478, 1062317] Funding Source: researchfish
- Medical Research Council [MC_UP_A600_1110] Funding Source: researchfish
- Medical Research Council [MC_UP_A600_1110] Funding Source: Medline
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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.
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