EGFR-IN-200

EGFR-IN-200 is an inhibitor targeting EGFR, TNF-α, and the IL-6/GP130 complex, effectively interacting with human EGFR (IC50=0.03 μM), TNF-α (IC50=3.1 μM), and the IL-6/GP130 complex (IC50=1.6 μM). It binds the ATP pocket of EGFR, the trimer interface of TNF-α, and the cytokine-receptor interface of IL-6/GP130, inducing cell cycle G2/M phase arrest, apoptosis, and antiproliferative effects. EGFR-IN-200 is characterized by high gastrointestinal absorption and low blood-brain barrier permeability, adhering to Lipinski's rules. It is applicable in research on lung cancer and breast adenocarcinoma.

EGFR-IN-200 (compound 5h) is a potent inhibitor of the viability of A549 and MCF-7 cancer cells, exhibiting IC50 values of 9.2 μM and 8.2 μM, respectively, and demonstrates high selectivity for malignant cells over non-tumorigenic cells. At concentrations ranging from 0.01 to 100 μM over 1 hour, EGFR-IN-200 effectively inhibits EGFR tyrosine kinase activity with an IC50 of 0.03 μM, surpassing the activity of Erlotinib. Additionally, EGFR-IN-200 directly binds to TNF-α and IL-6, with dissociation constants (Kd) of 2.3 μM and 1.8 μM, respectively. It induces G2/M phase cell cycle arrest in A549 cells, halts pre-mitotic progression, and initiates apoptosis with a total apoptosis rate of 82.15%, showing a preference for early-stage apoptosis.