A high-throughput cell-based screening for L858R/T790M mutant epidermal growth factor receptor inhibitors

Wen Hsing Lin, Song Jen-Shin, Tzu Wen Lien, Chun Yu Chang, Szu Huei Wu, Yu Wen Huang, Teng Yuan Chang, Ming Yu Fang, Kuei Jung Yen, Chun Hwa Chen, Chang Ying Chu, Hsing Pang Hsieh, Yi Rong Chen, Yu Sheng Chao, John T.A. Hsu

Research output: Contribution to journalArticlepeer-review

3 Citations (Scopus)

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 L858RIT790M 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.

Original languageEnglish
Pages (from-to)147-151
Number of pages5
JournalAnticancer research
Volume32
Issue number1
Publication statusPublished - 2012 Jan

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

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