Inhibition of EGFR Signaling by N-cyclohexyl-2-(1-(phenylsulfonyl)piperidin-4-yl) acetamide

Background: The epidermal growth factor receptor (EGFR) is a driver oncogene and specific blockade of EGFR has been shown to be an effective therapeutic approach against multiple human cancers.

Aims: Here we employed the homogeneous time-resolved fluorescence (HTRF) technology to screen new EGFR mediators.

Method: 4 hits (NDS-41107, NDS-41119, NDS-41111 and NDS-41126) were confirmed in a compound library of 8000 compounds, and the IC50 values were determined to be 15.45±2.25µM (NDS-41107), 6.16±0.88 µM (NDS-41119), 11.33±3.31 µM (NDS-41111) and 11.19±1.67µM (NDS-41126), respectively. We then showed that NDS-41119 (N-cyclohexyl-2-(1-(phenylsulfonyl) piperidin-4-yl) acetamide) significantly inhibited EGFR signaling in human lung cancer cells, as evidenced by decreased phosphorylation of EGFR、ERK and Akt. NDS-41119 also attenuated EGF-induced cell proliferation and migration in a dose-dependent manner. We finally demonstrated that NDS-41119 inhibited the T790M mutation in NCI-H1975 cells and potentiated the effect of gefitinib against resistant cells.

Result: Our results will contribute to the development of novel EGFR-targeted anti-cancer drugs.

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