Approaches to target tractability assessment - a practical perspective

Abstract

The assessment of the suitability of novel targets to intervention by different modalities, e.g. small molecules or antibodies, is increasingly seen as important in helping to select the most progressable targets at the outset of a drug discovery project. This perspective considers differing aspects of tractability and how it can be assessed using in silico and experimental approaches. We also share some of our experiences in using these approaches.

Fig. 1. A schematic representation of the biology (vertical axis) and chemistry (horizontal axis) contributions to the overall concept of druggability.

Fig. 2. The gene buckets of tractability for small molecules (SM). The main differences between the tractability buckets for SM and antibodies (mAB) are highlighted in the boxes on the right. Human genome defined as all protein coding genes, and extracted from NCBI in November 2016. For more detailed rules see Appendix.

Fig. 3. Confusion matrix for two class model of tractability prediction based on SiteMap Dscore values obtained for 70 unique proteins. Accuracy = 0.79, CI = (0.67, 0.87).