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Chemical Biology Core Facility

Chemical Biology Core Facility

Ligand docked into target protein

The facility assists groups in developing primary and secondary assays for screening against the in-house compound library and guide them in developing tool compounds for their specific target.

Small molecules play essential roles in many areas of basic research and are often used to address important biological questions. Our aim is to enable research groups to address biological questions by identifying and developing ‘biotool’ compounds against novel targets. We can assist groups in the development of primary and secondary assays for screening against our in-house compound library and guide them through the process of developing tool compounds for their specific target. Chemical optimisation projects can be done in collaboration with our chemistry partners. The facility is a collaboration between EMBL, the German Cancer Research Center (DKFZ), and the University of Heidelberg (since February 2012) to provide the infrastructure and expertise to open up small molecule development to research groups at these institutions.

Major projects and accomplishments

The facility was established at the beginning of 2004. We have a very strong pipeline of projects from all three institutes covering biochemical- and cell-based targets. At the end of 2009 we established computational chemistry as part of the facility offering. Elara Pharmaceuticals GmbH and Savira Pharmaceuticals GmbH have been founded to further develop and commercialise active compounds identified in the facility, targeting specific cancer cell signalling pathways and the influenza virus respectively.

Services provided

Our screening library is composed of around 80 000 compounds. The selection focused on compound catalogues from three leading vendors in the field. Each vendor offers access to significantly larger collections, with low redundancy and highly competitive prices, coupled with attractive options for resupply and follow-up synthesis services. Selected compounds were checked for drug-likeness, structural and shape diversity, novelty, and compliance with medicinal chemistry requirements.

Individual compound selection was done by picking representative compounds around selected scaffolds. A scaffold-based selection offers the advantage of high information screening: as the structural space around each scaffold is covered appropriately, any hit compounds from a high throughput screen can be rapidly followed up by selecting similar compounds to enable initial structure-activity relationships to be discerned. This will help in the prioritisation of the hit compounds for further medicinal chemistry optimisation.

Further services include:

  • Selection of appropriate assay technology platforms.
  • Developing assays for medium throughput screening.
  • Assisting in the design of secondary specificity assays.
  • Compound characterisation.
  • Managing compound acquisition through our chemistry partners.
  • Computational screening using ligand-based and structure-based design strategies.

Partners

  • Technology partners: Perkin Elmer, IDBS, Certara, GE, TTP Labtech.
  • Chemistry partners: ChemDiv, Chembridge and Enamine.