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• W2800331393 abstract "// Cheng-Han Yu 1 , Chi-Chi Chou 2 , Hsin-Fang Tu 3 , Wei-Chieh Huang 1 , Ya-Yeh Ho 1 , Kay-Hooi Khoo 1, 2 , Ming-Shyue Lee 3 and Geen-Dong Chang 1 1 Graduate Institute of Biochemical Sciences, College of Life Science, National Taiwan University, Taipei 10617, Taiwan 2 Institute of Biological Chemistry, Academia Sinica, Taipei 11529, Taiwan 3 Department of Biochemistry and Molecular Biology, College of Medicine, National Taiwan University, Taipei 100, Taiwan Correspondence to: Geen-Dong Chang, email: gdchang@ntu.edu.tw Ming-Shyue Lee, email: mslee2006@ntu.edu.tw Keywords: afatinib; target identification; ribonucleotide reductase; covalent drug; gemcitabine Received: October 29, 2017      Accepted: April 05, 2018      Published: April 20, 2018 ABSTRACT Afatinib, used for the first-line treatment of non-small-cell lung carcinoma (NSCLC) patients with distinct epidermal growth factor receptor (EGFR) mutations, inactivates EGFR by mimicking ATP structure and forming a covalent adduct with EGFR. We developed a method to unravel potential targets of afatinib in NSCLC cells through immunoprecipitation of afatinib-labeling proteins with anti-afatinib antiserum and mass spectrometry analysis. Ribonucleotide reductase (RNR) is one of target proteins of afatinib revealed by this method. Treatment of afatinib at 10-100 nM potently inhibited intracellular RNR activity in an in vitro assay using permeabilized PC-9 cells (formerly known as PC-14). PC-9 cells treated with 10 μM afatinib displayed elevated markers of DNA damage. Long-term treatment of therapeutic concentrations of afatinib in PC-9 cells caused significant decrease in protein levels of RNR subunit M2 at 1-10 nM and RNR subunit M1 at 100 nM. EGFR-null Chinese hamster ovary (CHO) cells treated with afatinib also showed similar effects. Afatinib repressed the upregulation of RNR subunit M2 induced by gemcitabine. Covalent modification with afatinib resulting in inhibition and protein downregulation of RNR underscores the therapeutic and off-target effects of afatinib. Afatinib may serve as a lead compound of chemotherapeutic drugs targeting RNR. This method can be widely used in the identification of potential targets of other covalent drugs." @default.
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• W2800331393 date "2018-04-20" @default.
• W2800331393 modified "2023-10-16" @default.
• W2800331393 title "Antibody-assisted target identification reveals afatinib, an EGFR covalent inhibitor, down-regulating ribonucleotide reductase" @default.
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• W2800331393 cites W1507250986 @default.
• W2800331393 cites W1527742565 @default.
• W2800331393 cites W1555309303 @default.
• W2800331393 cites W1645126533 @default.
• W2800331393 cites W1659527116 @default.
• W2800331393 cites W1795204252 @default.
• W2800331393 cites W1973109316 @default.
• W2800331393 cites W1976385056 @default.
• W2800331393 cites W1977179006 @default.
• W2800331393 cites W1978380670 @default.
• W2800331393 cites W1984353977 @default.
• W2800331393 cites W1990010967 @default.
• W2800331393 cites W1992553266 @default.
• W2800331393 cites W1995242599 @default.
• W2800331393 cites W1999250507 @default.
• W2800331393 cites W1999318478 @default.
• W2800331393 cites W2008126023 @default.
• W2800331393 cites W2010993054 @default.
• W2800331393 cites W2024502310 @default.
• W2800331393 cites W2024908724 @default.
• W2800331393 cites W2027504487 @default.
• W2800331393 cites W2038882649 @default.
• W2800331393 cites W2041252925 @default.
• W2800331393 cites W2041998379 @default.
• W2800331393 cites W2043696829 @default.
• W2800331393 cites W2045158653 @default.
• W2800331393 cites W2048766149 @default.
• W2800331393 cites W2057079741 @default.
• W2800331393 cites W2057458801 @default.
• W2800331393 cites W2063391304 @default.
• W2800331393 cites W2065141010 @default.
• W2800331393 cites W2067168610 @default.
• W2800331393 cites W2071549499 @default.
• W2800331393 cites W2074061743 @default.
• W2800331393 cites W2079688459 @default.
• W2800331393 cites W2085490150 @default.
• W2800331393 cites W2085800738 @default.
• W2800331393 cites W2096198395 @default.
• W2800331393 cites W2100631929 @default.
• W2800331393 cites W2107565528 @default.
• W2800331393 cites W2108655890 @default.
• W2800331393 cites W2114095518 @default.
• W2800331393 cites W2114163388 @default.
• W2800331393 cites W2118113452 @default.
• W2800331393 cites W2118443127 @default.
• W2800331393 cites W2125760261 @default.
• W2800331393 cites W2128930132 @default.
• W2800331393 cites W2129656399 @default.
• W2800331393 cites W2132870547 @default.
• W2800331393 cites W2138851777 @default.
• W2800331393 cites W2139236349 @default.
• W2800331393 cites W2142007492 @default.
• W2800331393 cites W2151792234 @default.
• W2800331393 cites W2153243769 @default.
• W2800331393 cites W2154066874 @default.
• W2800331393 cites W2161821474 @default.
• W2800331393 cites W2163054872 @default.
• W2800331393 cites W2164530678 @default.
• W2800331393 cites W2167854315 @default.
• W2800331393 cites W2168967690 @default.
• W2800331393 cites W2171139285 @default.
• W2800331393 cites W2176184837 @default.
• W2800331393 cites W2292347930 @default.
• W2800331393 cites W2346398506 @default.
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• W2800331393 doi "https://doi.org/10.18632/oncotarget.25177" @default.
• W2800331393 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/5940374" @default.
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