EGFR-IN-201

EGFR-IN-201 is a potent EGFR inhibitor with an IC50 of 0.091 μM for wild-type EGFR. For mutant EGFR variants, EGFRT790M, EGFRL858R, and EGFRC797S, it exhibits IC50 values of 0.147 μM, 0.221 μM, and 0.703 μM, respectively. EGFR-IN-201 also inhibits downstream signaling proteins AKT1 (IC50 = 0.225 μg/mL) and ERK1 (IC50 = 0.705 μg/mL). The compound can induce G0/G1 phase cell cycle arrest, apoptosis, and low-level necrosis in cancer cells. EGFR-IN-201 is applicable in cancer research, including studies on colon cancer.

EGFR-IN-201 (Compound 5c), at concentrations ranging from 0.01 to 100 μM, effectively inhibits the growth of NCI-60 cancer cell lines, displaying GI₅₀ values between 2.77 and 20.70 μM, and exhibits strong activity against various solid and hematological tumors. At 19.60 µM, EGFR-IN-201 induces G0/G1 phase cell cycle arrest in human colon adenocarcinoma cells (HT-29), significantly promotes apoptosis (total of 26.51%), and moderately elevates necrosis levels in these cells. This compound enhances apoptosis-related gene expression in HT-29 cells by upregulating caspase-3, caspase-9, and Bax while downregulating Bcl-2, resulting in a 14.1-fold increase in the Bax/Bcl-2 ratio. Additionally, EGFR-IN-201 shows low cytotoxicity towards normal human lung fibroblasts (WI-38), with an IC₅₀ of 51.903 μM, indicating a favorable safety profile compared to cancer cells.