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ToBeLi-for-GPR3-6-12

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Towards high-affinity ligands for orphan receptors GPR3, GPR6 & GPR12

The family of G protein-coupled receptors (GPCRs) comprises more than 800 human cell surface receptors that perceive and transmit extracellular stimuli into the cell interior. Due to their involvement in numerous biochemical proce... ver más

31/07/2024

UMR

Presupuesto desconocido

Líder del proyecto

PHILIPPS UNIVERSITAET MARBURG No se ha especificado una descripción o un objeto social para esta compañía.

TRL 4-5

Fecha límite participación Sin fecha límite de participación.

Financiación concedida El organismo HORIZON EUROPE notifico la concesión del proyecto el día 2024-07-31

HORIZON-MSCA-2021-PF-01-01: MSCA Postdoctoral Fellowships 2021 ExpectedOutcome:

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Cerrada hace 3 años

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Duración del proyecto: 25 meses Fecha Inicio: 2022-06-01
Fecha Fin: 2024-07-31

Líder del proyecto

PHILIPPS UNIVERSITAET MARBURG No se ha especificado una descripción o un objeto social para esta compañía.

TRL 4-5

Fecha límite de participación Sin fecha límite de participación.

Descripción del proyecto The family of G protein-coupled receptors (GPCRs) comprises more than 800 human cell surface receptors that perceive and transmit extracellular stimuli into the cell interior. Due to their involvement in numerous biochemical processes, GPCRs represent prime targets for the treatment of various diseases and are modulated by more than 30% of approved drugs today. However, a large proportion of the druggable GPCRome remains pharmacologically untapped, including the so-called ‘orphan’ GPCRs (oGPCRs) - receptors for which the endogenous ligands remain unknown.GPR3, 6 and 12 constitute a cluster of orphan GPCRs that is involved in numerous (patho-)physiological processes including neurodegenerative disorders such as Parkinson’s and Alzheimer’s dementia. GPR3 and GPR12 further mediate meiotic arrest in oocytes and suppress the development of metabolic diseases. Other physiological processes and diseases associated with GPR3/6/12 are neuropathic pain perception, addiction and different forms of cancer. Although these receptors represent promising pharmacological targets and researchers have been trying to discover molecules targeting these receptors for more than two decades, only a limited set of five ligands is currently available. Modern GPR3/6/12-targeted drug discovery is still hampered by the lack of verified endogenous ligands, our poor understanding of their structural organization and signalling cascades promoted by these receptors, and a limited panel of assays revealing GPR3/6/12 activity in living cells.Here, I propose to implement an interdisciplinary research approach combining computational methodologies with advanced biosensor technology in order to discover advanced ligands for these attractive drug targets. These novel compounds will aid in developing advanced therapeutics tackling severe human diseases and our reseach will highlight the power of interdisciplinary drug discovery approaches, promoting their implementation in the GPCR field and beyond.

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