ABSTRACT: A series of new multi-target inhibitors derived from quinazoline and 1,3,4-oxadiazole-2-thione were designed, synthesized, and tested in vitro for their antiproliferative efficacy. Compounds 7a, 7e, 7h, 7k, and 7l exhibited the most significant antiproliferative activity, with GI50 values of 30, 26, 39, 35, and 32 nM, respectively. The in vitro inhibitory effects of compounds 7a, 7e, 7h, 7k, and 7l against the EGFR, BRAFV600E, and HER-2 isozymes were examined. Compounds 7h and 7k were identified as the most potent multi-target inhibitors, with IC50 values of 76 ± 4 (EGFR), 33 ± 2 (HER-2), and 48 ± 3 (BRAFV600E) for 7h, and 71 ± 4 (EGFR), 29 ± 1 (HER-2), and 45 ± 3 (BRAFV600E) for 7k, respectively. Compounds 7h and 7k mark