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

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.

journal_name

Anticancer Res

journal_title

Anticancer research

authors

Lin WH,Song JS,Lien TW,Chang CY,Wu SH,Huang YW,Chang TY,Fang MY,Yen KJ,Chen CH,Chu CY,Hsieh HP,Chen YR,Chao YS,Hsu JT

subject

Has Abstract

pub_date

2012-01-01 00:00:00

pages

147-51

issue

1

eissn

0250-7005

issn

1791-7530

pii

32/1/147

journal_volume

32

pub_type

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