title: Inhibition of EGFR Signaling by N-cyclohexyl-2-(1-(phenylsulfonyl)piperidin-4-yl) acetamide.
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.
  
  
  OBJECTIVE
  Here we employed the homogeneous time-resolved fluorescence (HTRF) technology to screen new EGFR mediators.
  
  
  METHODS
  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.
  
  
  RESULTS
  Our results will contribute to the development of novel EGFR-targeted anti-cancer drugs.
authors.affiliation: Jiangsu Key Laboratory of Drug Screening, China Pharmaceutical University, Nanjing 210009, China.
authors.forename: Sensen
authors.initials: S
authors.lastname: Lin
authors.affiliation: Jiangsu Key Laboratory of Drug Screening, China Pharmaceutical University, Nanjing 210009, China.
authors.forename: Hang
authors.initials: H
authors.lastname: Li
authors.affiliation: Jiangsu Cancer Hospital, Nanjing 210009, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Yu
authors.affiliation: Jiangsu Key Laboratory of Drug Screening, China Pharmaceutical University, Nanjing 210009, China.
authors.forename: Luyong
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Jiangsu Key Laboratory of Drug Screening, China Pharmaceutical University, Nanjing 210009, China.
authors.forename: Ming
authors.initials: M
authors.lastname: Yan
authors.affiliation: Jiangsu Center for Pharmacodynamics Research and Evaluation, China Pharmaceutical University, Nanjing 210009, China.
authors.forename: Hongyang
authors.initials: H
authors.lastname: Li
authors.affiliation: Jiangsu Center for Pharmacodynamics Research and Evaluation, China Pharmaceutical University, Nanjing 210009, China.
authors.forename: Xinxin
authors.initials: X
authors.lastname: Li
authors.affiliation: Jiangsu Center for Pharmacodynamics Research and Evaluation, China Pharmaceutical University, Nanjing 210009, China.
authors.forename: Shengtao
authors.initials: S
authors.lastname: Yuan
authors.affiliation: Jiangsu Center for Pharmacodynamics Research and Evaluation, China Pharmaceutical University, Nanjing 210009, China.
authors.forename: Li
authors.initials: L
authors.lastname: Sun
mesh_terms: D000081:Acetamides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D066246:ErbB Receptors / Q000037:antagonists & inhibitors* / Q000378:metabolism; D031541:Fluorescence Resonance Energy Transfer; D006801:Humans; D015394:Molecular Structure; D047428:Protein Kinase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects*; D013329:Structure-Activity Relationship; D013449:Sulfonamides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000081:Acetamides; D000970:Antineoplastic Agents; C000625646:N-cyclohexyl-2-(1-(phenylsulfonyl)piperidin-4-yl)acetamide; D047428:Protein Kinase Inhibitors; D013449:Sulfonamides; C512478:EGFR protein, human; D066246:ErbB Receptors
keywords: EGFR; HTRF; cell migration; cell proliferation; gefitinib.; lung cancer