Identification and preliminary characterization of novel small molecules that inhibit growth of human lung adenocarcinoma cells Journal Article
| Authors: | Somwar, R.; Shum, D.; Djaballah, H.; Varmus, H. |
| Article Title: | Identification and preliminary characterization of novel small molecules that inhibit growth of human lung adenocarcinoma cells |
| Abstract: | Drug treatment for human lung cancers remains unsatisfactory, despite the identification of many potential therapeutic targets (such as mutant KRAS protein) and the approval of agents that inhibit the tyrosine kinase activity of mutant epidermal growth factor receptor (EGFR). To seek new therapeutic strategies against lung tumors, the authors have screened 189,290 small molecules for their ability to retard growth of human lung adenocarcinoma cell lines, which harbor mutations in EGFR or KRAS. Four candidates that are structurally different from common tyrosine kinase inhibitors were selected for further study. The authors describe one small molecule (designated lung cancer screen-1 [LCS-1]) in detail here. Identification of the targets of LCS-1 and other growth inhibitors found in this screen may help to develop new agents for the treatment of lung adenocarcinomas, including those driven by mutant EGFR and KRAS. © 2009 Society for Biomolecular Sciences. |
| Keywords: | signal transduction; mitogen activated protein kinase; controlled study; protein phosphorylation; unclassified drug; gene mutation; human cell; antineoplastic agents; antineoplastic agent; dna synthesis; adenocarcinoma; cell proliferation; cell survival; apoptosis; gene expression; lung neoplasms; epidermal growth factor receptor; lung cancer; receptor, epidermal growth factor; antineoplastic activity; drug screening assays, antitumor; enzyme activity; small molecule libraries; cell line, tumor; phosphorylation; phosphatidylinositol 3 kinase; cancer inhibition; lung adenocarcinoma; cancer cell; 1-phosphatidylinositol 3-kinase; dna, neoplasm; gefitinib; egfr; kras; oncogene k ras; drug half life; ic 50; mitogen-activated protein kinases; half-life; high-throughput drug screen; 2 phenylpyridazin 3(2h) one derivative; pyridazinone derivative; liver microsome; hydrazines; microsomes, liver |
| Journal Title: | Journal of Biomolecular Screening |
| Volume: | 14 |
| Issue: | 10 |
| ISSN: | 1087-0571 |
| Publisher: | Sage Publications |
| Date Published: | 2009-12-01 |
| Start Page: | 1176 |
| End Page: | 1184 |
| Language: | English |
| DOI: | 10.1177/1087057109350919 |
| PUBMED: | 19887599 |
| PROVIDER: | scopus |
| PMCID: | PMC3146390 |
| DOI/URL: | |
| Notes: | --- - "Export Date: 30 November 2010" - "CODEN: JBISF" - "Source: Scopus" |
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