| Summary: | A novel series of hybrid compounds comprising quinazolin-4-one and 3-cyanopyridin-2-one structures has been developed, with dual inhibitory actions on both EGFR and BRAF<sup>V600E</sup>. These hybrid compounds were tested in vitro against four different cancer cell lines. Compounds <b>8</b>, <b>9</b>, <b>18</b>, and <b>19</b> inhibited cell proliferation significantly in the four cancer cells, with GI<sub>50</sub> values ranging from 1.20 to 1.80 µM when compared to Doxorubicin (GI<sub>50</sub> = 1.10 µM). Within this group of hybrids, compounds 18 and 19 exhibited substantial inhibition of EGFR and BRAF<sup>V600E</sup>. Molecular docking investigations provided confirmation that compounds <b>18</b> and <b>19</b> possess the capability to inhibit EGFR and BRAF<sup>V600E</sup>. Moreover, computational ADMET prediction indicated that most of the newly synthesized hybrids have low toxicity and minimal side effects.
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