Title: A High-throughput Cell-based Screening for L858R/T790M Mutant Epidermal Growth Factor Receptor Inhibitors
Authors: Lin, Wen-Hsing
Song, Jen-Shin
Lien, Tzu-Wen
Chang, Chun-Yu
Wu, Szu-Huei
Huang, Yu-Wen
Chang, Teng-Yuan
Fang, Ming-Yu
Yen, Kuei-Jung
Chen, Chun-Hwa
Chu, Chang-Ying
Hsieh, Hsing-Pang
Chen, Yi-Rong
Chao, Yu-Sheng
Hsu, John T-A
Department of Biological Science and Technology
Keywords: HTS;EGFR;non-small cell lung cancer (NSCLC);TKI
Issue Date: 1-Jan-2012
Abstract: A high-throughput 32D(L858R/T790M) cell-based assay to identify inhibitors of the L858R/T790M mutant epidermal growth factor receptor (EGFR) pathway was established. After screening, ten hits from among 60,000 compounds in our in-house compound library were initially identified. In the secondary assays, one hit, 1-[2-(decyloxy)-2-oxoethyl]-3-methyl-2-[(4-methylphenoxy) methyl]-1H-benzimidazol-3-ium, was confirmed to directly inhibit the kinase activity of recombinant L858R/T790M EGFR and the phosphorylation of EGFR-L858R/T790M in gefitinib-resistant H1975 cells. Thus, this high-throughput assay system may be useful for identifying novel inhibitors which suppress mutant EGFR-T790M signalling and for overcoming T790M-mediated acquired resistance for future anticancer drug discovery.
URI: http://hdl.handle.net/11536/15334
ISSN: 0250-7005
Volume: 32
Issue: 1
Begin Page: 147
End Page: 151
Appears in Collections:Articles