Large Scale Druggability Screening

We and others (e.g. Hajduk et al, 2005, J. Med. Chem, 48, p. 2518; Edfeldt et al., 2011 Drug Discovery Today, 16(7), p. 284) have noted a strong correlation between the hit rate (and hit diversity) in NMR fragment screening and the “druggability” of a target. ZoBio has developed its own correlation between TINS and druggability as shown in the figure on our website. In TINS, binding is best represented by the ratio of the heights of each peak of a compound in the presence of the reference and the target (the T/R ratio). Each of these graphs presents the number of compounds with a T/R in each of the bins presented on the x-axis. This gives a profile of the screen that is unique for each target. The figure demonstrates how the profile varies with the known druggability of three different targets.

The scheme presented will allow large scale (15-20 targets/yr), efficient fragment screening on targets at a very early stage in the drug discovery process (e.g. before HTS and even before a purification strategy has been developed). In this way early prioritization based on data can be made, HTS results can be more intelligently interpreted and FBDD can have an early start.