A set of kinase inhibitor candidates for ROS1 was available from Janssen, which comprises 150 compounds from an internal ROS1 inhibition lead optimization program. The compounds are numbered as per the order in the file provided by Janssen. They are all based on the same chemical scaffold, a tetrahydropyrazolopyrazinone (Figure ). The ROS1 activity is provided from a biochemical substrate inhibition assay and a cell proliferation assay. The former is preferred here for comparing with calculated binding free energies. The pIC50 of the compounds ranged from 5.03 to 8.37, a total of 3.34 log units (no activity was detected for five of the compounds at the highest concentration (10 μM) tested; a pIC50 of 5.00 was used hereafter). To capture the experimental variability, we extracted all data for repeat bioactivity measurements of the same compound in the same assay. The average standard deviation in pIC50 for compounds tested at least twice in the ROS1 biochemical assay was 0.12 log units. This is considered an underestimate of the true experimental error which should also include considerations of new compound samples, different assay conditions and laboratories etc.