Community Research and Development Information Service - CORDIS


DE-ORPHAN Report Summary

Project ID: 639125
Funded under: H2020-EU.1.1.

Periodic Reporting for period 1 - DE-ORPHAN (DEtermination of Orphan Receptor PHysiological Agonists and sigNals)

Reporting period: 2015-05-01 to 2016-10-31

Summary of the context and overall objectives of the project

G protein-coupled receptors make up both the largest membrane protein and drug target families. DE-ORPHAN aims to determine the close functional context; specifically physiological agonists and signaling pathways; and provide the first research tool compounds, of orphan peptide receptors. About one third of the human GPCRs are so called orphan receptors, meaning that their endogenous agonist (and function) is unknown. Characterisation of orphan receptors can unravel unknown physiological signalling systems and present new druggable targets, ligands and mechanisms. 

Work performed from the beginning of the project to the end of the period covered by the report and main results achieved so far

We apply computational methods to identify; physiological ligands that link the receptor to a physiological system, tool compounds for pharmacological characterisation, and G protein inhibitors for effective dissection of the intracellular signalling pathways.

In the first period, we have selected orphan receptor targets, set up pharmacological assays for 21 receptors, designed peptide and small molecule screening libraries. We have also synthesised naturally occurring inhibitors of the intracellular signalling G protein, and designed analogous thereof towards identifying selective probes for dissection of receptor signalling. Finally, we have initiated the work that will add our data and computational tools in a public community resource, GPCRdb (currently serving ~1500 monthly users).

So far, 5 peer-reviewed articles have been published in this project.

Progress beyond the state of the art and expected potential impact (including the socio-economic impact and the wider societal implications of the project so far)

The results will allow the research field to advance into studies of receptor functions and exploitation of druggable targets, ligands and mechanisms. Which physiological insights and therapeutic breakthroughs will we witness when these receptors find their place in human pharmacology and medicine?
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