Out of these 22 compounds, 10 were approved drugs -EGFRi but also pan-kinase and other inhibitorsand the rest were either preclinical or clinical candidates (Supplementary Figure ). The first two generations of EGFRi were represented in this analysis. The rest of the molecules can be found in Supplementary Figure . The biggest ring system in each molecule is highlighted in red for reference as a less stringent proxy for the maximum common substructure to visually distinguish molecules with similar scaffolds. Variants are further represented by the distance from the substituted residue to the centroid of the ligand in the structure of the protein and by the Epstein coefficient of difference calculated for the amino acid substitution. In variants with multiple substitutions reported, the average distance and Epstein coefficient of difference are reported.