A simple and rational method to rank molecules’ lead-likeness using continuous evaluation functions was developed to support epigenetic drug discovery. This strategy proved to be highly effective on model chemical libraries and finally helped drive synthetic efforts towards candidates of interest for epigenetic applications towards HDAC6, BRD4, and EZH2.

Here we provide sample data and the knime workflow for generating lead-like chemical probes for epigenetics. This tool and example data set will enable researchers to establish this workflow in their own laboratories and apply it to new synthetic scaffolds for medicinal chemistry.