Switching to the 3-cyanoquinoline scaffold, 4-((3-ethynylphenyl)amino)-6-iodoquinoline-3-carbonitrile (28) showed an improvement in potency in three of the four chordoma cell lines: CH22 (IC50 = 8.4 μM), UM-Chor1 (IC50 = 6.9 μM), and U-CH12 (IC50 = 7.7 μM), with only moderate non-specific toxicity in the WS1 control cells (IC50 = 34 μM) despite an eightfold reduction in EGFR activity compared to erlotinib. This evidence concerns the gene EGFR and chordoma.