About the network

SAFER is the first European research platform to gain a molecular understanding and improve selectivity in stimulation of the serotonin 5-HT2A receptor – the primary target for many CNS-related disorders and hallucinogens. SAFER will design and prepare ligands for the receptor, generate and cross-interpret pharmacology and crystallographic data, and construct computational mechanistic models and databases.

The SAFER network comprises five PhD students in pharmacology, chemistry, crystallography, computational drug design and scientific database development; first receiving 1-1,5 years joint training at the University of Copenhagen (Denmark) followed by industrial research at Enamine (Kiev, Ukraine) or SARomics (Lund, Sweden).

SAFER is coordinated by Jesper Kristensen at the University of Copenhagen who leads a chemistry group that has developed serotonin 5-HT2A receptor ligands being used as tracers for human brain imaging for diagnosis and evaluation of treatments.

Scientific Work Packages and Objectives

WP1: Selectivity mechanisms (Lead: SAR)
Provide a rationale for design of safer drugs by uncovering molecular mechanisms for functional selectivity of the serotonin 5-HT2A receptor. This will be achieved through integration of holistic pharmacological assaying, medicinal chemistry, crystallography and structure-based modelling.

WP2: Selective ligands (Lead: Enamine)
Identify patentable novel ligands with therapeutically favourable 5-HT2A signalling profile(s). This will be achieved through integration of molecular models, conformationally restricted analogues and signalling profiles obtained in WP1.

WP3: Public ligand resource (Lead: UPCH)
Develop a public GPCR ligand database including functionally selective agonists to disseminate SAFER results and enable new research in the wider GPCR community.