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

[ Vol. 17 , Issue. 11 ]

Author(s):

Sensen Lin, Hang Li, Jun Yu, Luyong Zhang, Ming Yan, Hongyang Li, Xinxin Li, Shengtao Yuan* and Li Sun*   Pages 1500 - 1507 ( 8 )

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.

Keywords:

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

Affiliation:

Jiangsu Key Laboratory of Drug Screening, China Pharmaceutical University, Nanjing 210009, Jiangsu Key Laboratory of Drug Screening, China Pharmaceutical University, Nanjing 210009, Jiangsu Cancer Hospital, Nanjing 210009, Jiangsu Key Laboratory of Drug Screening, China Pharmaceutical University, Nanjing 210009, Jiangsu Key Laboratory of Drug Screening, China Pharmaceutical University, Nanjing 210009, Jiangsu Center for Pharmacodynamics Research and Evaluation, China Pharmaceutical University, Nanjing 210009, Jiangsu Center for Pharmacodynamics Research and Evaluation, China Pharmaceutical University, Nanjing 210009, Jiangsu Center for Pharmacodynamics Research and Evaluation, China Pharmaceutical University, Nanjing 210009, Jiangsu Center for Pharmacodynamics Research and Evaluation, China Pharmaceutical University, Nanjing 210009

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