A comparison of the potency of cyano compounds I1‐I6 indicates that the benzyl group (R1) and 3.4‐dimethyl substituent on the Ar moiety are important structural elements for achieving strong anti‐cancer activity, thus identifying I4 as the most potent compound in this subseries with an IC50 value of 950.6 nm (Table S1, Supporting Information) against MDA‐MB‐231 cells and an Avg KD value of 692 nm binding to eEF2K protein in the SPR assay (Table S2, Supporting Information). The gene discussed is EEF2K; the disease is cancer.