DEtermination of Orphan Receptor PHysiological Agonists and sigNals

Información del proyecto

DE-ORPHAN

Identificador del acuerdo de subvención: 639125

DOI

10.3030/639125

Proyecto cerrado

Fecha de la firma de la CE 17 Abril 2015

Fecha de inicio 1 Mayo 2015

Fecha de finalización 30 Abril 2020

Financiado con arreglo a

• EXCELLENT SCIENCE - European Research Council (ERC)

Coste total

€ 1 499 926,25

Aportación de la UE

€ 1 499 926,25

Coordinado por

KOBENHAVNS UNIVERSITET
Denmark

Periodic Reporting for period 4 - DE-ORPHAN (DEtermination of Orphan Receptor PHysiological Agonists and sigNals)

Período documentado: 2019-11-01 hasta 2020-04-30

Resumen del contexto y de los objetivos generales del proyecto

G protein-coupled receptors (GPCR) make up both the largest signalling system and drug target families in human, thus of high importance for physiology and medicine. DE-ORPHAN has identified physiological agonist hormones and research tool compounds poorly characterised ‘orphan’ receptors. These receptor ligands open up for exploration of the new physiological signalling systems and present new druggable targets, ligands and mechanisms.

Trabajo realizado desde el comienzo del proyecto hasta el final del período abarcado por el informe y los principales resultados hasta la fecha

We have developed 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.

The main results are:
1. Discovery of physiological peptide hormones for five GPCRs (Foster et al., Cell 2019).
2. Tool compounds for three receptors that can be used to uncover their pharmacology and function.
3. Unique data and webserver tools in our open access database GPCRdb serving >4,000 users/mon.

So far, the project has led to 20 peer-reviewed articles, 15 invited conference talks by the PI and 4 workshops.

Avances que van más allá del estado de la técnica e impacto potencial esperado (incluida la repercusión socioeconómica y las implicaciones sociales más amplias del proyecto hasta la fecha)

The identified physiological and surrogate ligands open up for characterisation of these important receptors in terms of their function and therapeutic relevance/area. The open access GPCRdb resources is a unique dissemination of data and tools of relevance not only for this project, but the wide receptor community. In all, the results will allow the research field to advance into studies of receptor functions and exploitation of druggable targets, ligands and mechanisms.

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