Fragments

The last decade or so has witnessed a change of paradigm by Life Science companies, who have redirected their screening efforts for hit finding/identification from high throughput screening (HTS) to more modern and flexible techniques such as Fragment-Based Library Screening (FBLS) and DNA-encoded library Technology (DELT). Compared to expensive and often unfruitful HTS campaigns, Fragment-Based Library Screening offers much more flexibility and diversity in the hits identified, due to the small nature of fragments compared to more complex/evolved traditional screening compounds.

Technical advances in biophysical techniques, such as NMR spectroscopy, Surface Plasmon Resonance (SPR), MicroScale Thermophoresis (MST) and other, allow for the use of low molecular weight molecules (Fragments) with low affinity to be identified. Among the criteria governing the development of Fragment Based Drug Discovery, three considerations (MW ≤300, H-bond donors ≤3, H-bond acceptors ≤3, cLogP ≤3), along with rotatable bond count and calculated TPSA limits, are commonly accepted. Finally, it has been established that the targeting of demanding biological targets would require higher three-dimensionality (3D).