BACKGROUND: The Open Targets Platform integrates different data sources in order 
to facilitate identification of potential therapeutic drug targets to treat 
human diseases. It currently provides evidence for nearly 2.6 million potential 
target-disease pairs. G-protein coupled receptors are a drug target class of 
high interest because of the number of successful drugs being developed against 
them over many years. Here we describe a systematic approach utilizing the Open 
Targets Platform data to uncover and prioritize potential new disease 
indications for the G-protein coupled receptors and their ligands.
RESULTS: Utilizing the data available in the Open Targets platform, potential 
G-protein coupled receptor and endogenous ligand disease association pairs were 
systematically identified. Intriguing examples such as GPR35 for inflammatory 
bowel disease and CXCR4 for viral infection are used as illustrations of how a 
systematic approach can aid in the prioritization of interesting drug discovery 
hypotheses. Combining evidences for G-protein coupled receptors and their 
corresponding endogenous peptidergic ligands increases confidence and provides 
supportive evidence for potential new target-disease hypotheses. Comparing such 
hypotheses to the global pharma drug discovery pipeline to validate the approach 
showed that more than 93% of G-protein coupled receptor-disease pairs with a 
high overall Open Targets score involved receptors with an existing drug 
discovery program.
CONCLUSIONS: The Open Targets gene-disease score can be used to prioritize 
potential G-protein coupled receptors-indication hypotheses. In addition, 
availability of multiple different evidence types markedly increases confidence 
as does combining evidence from known receptor-ligand pairs. Comparing the 
top-ranked hypotheses to the current global pharma pipeline serves validation of 
our approach and identifies and prioritizes new therapeutic opportunities.