Fragment-Based Drug Discovery has developed into a significant alternative for identifying preliminary hits. Due to its design-driven nature, it facilitates the efficient development of novel leads. FBDD is an approach in which much lower molecular weight (MW) compounds are screened compared to HTS campaigns.
Fragment hits are typically weak binders with affinities in the μM to mM range and require screening at high concentrations. Conventional biochemical assays are usually limited due to high solvent content and not sensitive enough to identify potential hits.
Sensitive biophysical methods such as Nuclear Magnetic Resonance (NMR), Surface Plasmon Resonance (SPR), Temperature-Related Intensity Change (TRIC), Fluorescence Thermal Shift Assay (FTSA), Isothermal Titration Calorimetry (ITC), X-ray crystallography, Mass Spectrometry are essential to identify weak interactions between fragments and the target protein.
Given their high throughput capacities, SPR, MST/TRIC, and TSA are often used as the primary screening technology with ITC and X‐ray crystallography serving as secondary screening and validation.
With close collaboration of Biophysical Platform, the Protein Production Team provides custom-designed recombinant proteins tailored for specific biophysical methods, the Crystallography Team carries out X-ray structural studies, as well as with Medicinal and Computational Chemistry Teams which support design and synthesis of compounds from identified fragments, Selvita provides fully integrated scientifically-driven service in fragment-based screening.
If you want to learn more about our capabilities in this area, download a brochure with details HERE.