表皮生长因子受体（EGFR）和人类表皮生长因子受体2（HER2）蛋白酪氨酸激酶在各种癌症中共同表达，例如卵巢、乳腺、结肠和前列腺亚型。在此，新的TAK-285衍生物（9a-h）被合成、表征并被作为双重EGFR/HER2抑制剂进行生物学评价。化合物9f对EGFR和HER2分别表现出2.3 nM和234 nM的IC50值，这是staurosporine的38倍和TAK-285对EGFR的10倍。在小激酶面板上测试时，化合物9f也表现出很高的选择性。化合物9a-h对PC3和22RV1前列腺癌细胞株的IC50值分别在1.0-7.3 nM和0.8-2.8 nM之间。细胞周期分析、凋亡诱导、分子对接、动力学和MM-GBSA研究证实了化合物9f作为强效EGFR/HER2双重抑制剂的可能机制，并对前列腺癌具有有效的抗增殖作用。

Epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor 2 (HER2) protein tyrosine kinases co-expressed in various cancers such as ovarian, breast, colon, and prostate subtypes. Herein, new TAK-285 derivatives (9a-h) were synthesised, characterised, and biologically evaluated as dual EGFR/HER2 inhibitors. Compound 9f exhibited IC50 values of 2.3 nM over EGFR and 234 nM over HER2, which is 38-fold of staurosporine and 10-fold of TAK-285 over EGFR. Compound 9f also showed high selectivity profile when tested over a small kinase panel. Compounds 9a-h showed IC50 values in the range of 1.0-7.3 nM and 0.8-2.8 nM against PC3 and 22RV1 prostate carcinoma cell lines, respectively. Cell cycle analysis, apoptotic induction, molecular docking, dynamics, and MM-GBSA studies confirmed the plausible mechanism(s) of compound 9f as a potent EGFR/HER2 dual inhibitor with an effective antiproliferative action against prostate carcinoma.