Fragment-Based Drug Discovery (FBDD)

Fragment-based drug discovery (FBDD) focuses on smaller molecular fragments as starting points for drug design. They are systematically assembled to create larger, more complex molecules with enhanced binding affinity and specificity for the target protein.

FBDD allows for a highly efficient exploration of chemical space, enabling researchers to identify key interactions between fragments and target proteins. We successfully apply our FBDD screening services to drug discovery projects across multiple biological targets ranging from well characterized bromodomains to complex protein-protein interactions.

We are pushing the boundaries of chemical space sampling even further with our proprietary fragment collection, which contains the smallest fragments detectable using cutting-edge biophysics. This “biophysical” fragment collection samples the limits of the biophysically accessible chemical universe; providing exquisitely lean fragment hits.

A custom biophysical screening platform

Our team of biologists has access to and expertise in state-of-the-art instrumentation for biophysical screening. Our bespoke fragment screening workflow provides means to rapidly select and grow the best fragments:

• First pass screen: Surface Plasmon Resonance (Biacore 8K) or Grating Coupled Interferometry (GCI) waveRAPID® technology to identify primary hits
• ‍Deselection screen: SPR or GCI waveRAPID® using either denatured protein, a control protein or counter-target
• Confirmation of affinity and determination of binding kinetics: SPR-or GCI-driven multi-cycle kinetics
• ‍Orthogonal confirmation of affinity: Differential Scanning Fluorimetry (DSF), MicroScale Thermophoresis (MST) or Isothermal Titration Calorimetry (ITC) or alternative biochemical assays
• ‍Determination of binding topologies: Ligand-observed and protein-observed NMR, X-ray crystallography, CryoEM

Accelerating the fragment-to-lead process 

Our team of chemistry, biology and ADMET experts deploy a range of cutting-edge technologies to rapidly progress the most promising fragment hits into high-quality leads including:

• ‍Sparse Array design: rapid exploration of the chemical space around each fragment hit
• ‍Computational modelling: tease out fragment growth and merging opportunities
• ‍Comprehensive biophysics: monitor improvements in affinities, binding kinetics, thermodynamics and evolution in binding topologies