Epigenetic drug discovery: systematic assessment of chemical space

Aim: The druggability of epigenetic targets has prompted researchers to develop small-molecule therapeutics. However, no systematic assessment has ever been done to investigate the chemical space of epigenetic modulators. Herein, we report a comprehensive chemoinformatic analysis of epigenetic ligands from EpiDBase, HEMD, ChEMBL and PubChem databases. Results: Nearly, 0.45 × 10 6 ligands were analyzed for assay interference compounds, target profiling, drug-like properties and hit prioritization. After eliminating approximately 96,000 problematic compounds, the remaining 0.36 × 10 6 compounds were studied for their physicochemical distributions, principal component analysis and hit prioritization. More than 30% of assay interference compounds were determined for many proteins. Conclusion: This systematic assessment of epigenetic ligands will help in the enrichment of screening libraries with high-quality compounds and thus, the generation of efficacious drug candidates.