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

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

Volume: 17 Issue: 11

Author(s): Sensen Lin, Hang Li, Jun Yu, Luyong Zhang, Ming Yan, Hongyang Li, Xinxin Li, Shengtao Yuan*Li Sun*

Affiliation:

• Jiangsu Center for Pharmacodynamics Research and Evaluation, China Pharmaceutical University, Nanjing 210009,China

• Jiangsu Center for Pharmacodynamics Research and Evaluation, China Pharmaceutical University, Nanjing 210009,China

Keywords: EGFR, HTRF, cell proliferation, cell migration, lung cancer, gefitinib.

Abstract: 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.

Cite this article as:

Lin Sensen, Li Hang, Yu Jun , Zhang Luyong, Yan Ming , Li Hongyang , Li Xinxin , Yuan Shengtao*, Sun Li *, Inhibition of EGFR Signaling by N-cyclohexyl-2-(1-(phenylsulfonyl)piperidin-4-yl) acetamide, Anti-Cancer Agents in Medicinal Chemistry 2017; 17 (11) . https://dx.doi.org/10.2174/1871520617666170327125251