Fragment-based ligandability screens

Table 3.2 Some of the targets against which fragment-based ligandability screens were run at AstraZeneca.

Keywords VS, Virtual Screening, Lead discovery, lead, HTS, Pharmacophore-Based, Structure-Based, Fragment-based, Ligand-based, Docking, Scoring, hybrid workflows, VS strategy, Benchmarking VS... 

We have used a highly structure-driven approach composed of fragment-based NMR screening, X-ray crystallography, and structure-assisted chemistry to develop a first-in-class clinical candidate as a potential proof-of-concept for the inhibition of BACE-1 in AD. Crucial to this achievement was the initial identification of a ligand-efficient isothiourea fragment and its X-ray crystal structure, which revealed an extensive H-bond network with the two active site aspartates. This interaction was unprecedented in the aspartic acid protease field when we discovered it several... 

Key words Fragment-based drug design, fragment screening, ligand efficiency, NMR, X-ray... 

Fragment-based screening can also identify more optimal matches (higher ligand efficiency) to the receptor without the need first to deconstruct a hit compound. 

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