Serotonin, or 5-hydroxytryptamine (5-HT), is a neurotransmitter that combines the effects of regulation of mood, appetite, and sleep, with effects on cognitive functions, like memory and learning. The serotonergic system is very complex, comprising 14 different receptor subtypes: 13 G protein-coupled receptors (GPCRs) and one ligand-gated ion channel. The SAFER project has a particular focus on the 5-HT2A receptor subtype, which is a validated drug target in the treatment of schizophrenia and other psychoses, cluster headaches, and glaucoma.
Accumulating clinical evidence suggests that 5-HT2A receptor agonists can relieve the suffering of treatment resistant depressive patients and anxiety in terminal ill cancer patients. However, their therapeutic mode of action is currently poorly understood due to low selectivity of available drugs. Furthermore, the impact of selectively on the activation of different signaling pathways of the 5-HT2A receptor is unknown, suggesting that there is an urgent need for identifying new functionally selective ligands.
Recent developments in GPCR pharmacology have shown that agonists can exhibit functional selectivity by preferentially triggering alternative intracellular signaling pathways. The SAFER project will exploit this mechanism to identify functionally Selective Agonists For the 5-HT2A sErotonin Receptor. Combining the knowledge accumulated at the University of Copenhagen about the development of ligands for the 5-HT2A receptor, GPCR pharmacology, molecular modeling and database development, with Examine’s extensive chemistry know-how and SARomics Biostructures’ structural biology platform, SAFER is well positioned to address this important scientific and societal challenge.
The SAFER project will train five PhD students in pharmacology, chemistry, crystallography, computational drug design and scientific database development. The consortium members include University of Copenhagen (Denmark), SARomics Biostructures (Sweden) and Enamine (Ukraine).
PhD4GlycoDrug: Multidisciplinary European Joint Doctorate in the Design and Development of Glyco Drugs
The PhD4GlycoDrug consortium has a main goal to offer a European Joint Doctorate educational training network in Glyco-Drug Discovery and Development. The network combines 6 academic partners with long tradition in PhD training and accredited doctoral studies in Organic Chemistry, Medicinal Chemistry, Structural Biology and Pharmacology/Pharmacy. Non-academic partners, 4 SMEs and a research institute also constitute the consortium to offer intersectoral exposure and quality training in transferable skills to entrepreneurial ESRs. So far, only a handful of registered drugs originate from glycoscience area. To pursue an innovative research project in such a timely scientific field of great interest for pharmaceutical industry, a specific set of competences is needed. Our network will focus on delivering expert researchers highly attractive for employment by the European Pharma-industry.