Plant‐Derived Anticancer Candidates Targeting mTOR, EGFR, HER2: Insights From Molecular Docking and Dynamics Simulations

In intracellular signaling, mammalian target of rapamycin (mTOR) as an important mammalian target for breast cancer therapy, plays a key role in receiving upstream signals from growth factor receptors such as epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor 2 (HER2). Using 30 compounds from Meehania fargesii var. Radicans, structure‐based virtual screening and molecular docking were performed to develop novel and safe breast cancer targeting inhibitors from natural products. Furthermore, the anti‐MCF‐7 effects of lower‐ranked ( 23 – 25 ) and top‐ranked compounds ( 26 – 30 ) in vitro showed that compound 28 (nepetoidin B) exhibited the strongest inhibitory effect on MCF‐7 proliferation with IC 50 value of 8.47 ± 0.85 µM. Besides, the dynamic behavior and interaction mode of 28 with mTOR, HER2, and EGFR were performed by molecular dynamics simulation, which sustain nepetoidin B bound stably to these druggable targets.