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.
authors.affiliation: Cancer Biology and Genetics Program, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA. somwarr@mskcc.org
authors.forename: Romel
authors.initials: R
authors.lastname: Somwar
authors.forename: David
authors.initials: D
authors.lastname: Shum
authors.forename: Hakim
authors.initials: H
authors.lastname: Djaballah
authors.forename: Harold
authors.initials: H
authors.lastname: Varmus
mesh_terms: D000230:Adenocarcinoma / Q000201:enzymology / Q000473:pathology*; D000970:Antineoplastic Agents / Q000032:analysis* / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004273:DNA, Neoplasm / Q000096:biosynthesis; D004354:Drug Screening Assays, Antitumor; D066246:ErbB Receptors / Q000378:metabolism; D006207:Half-Life; D006801:Humans; D006834:Hydrazines / Q000737:chemistry / Q000494:pharmacology; D008175:Lung Neoplasms / Q000201:enzymology / Q000473:pathology*; D008862:Microsomes, Liver / Q000187:drug effects / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects; D054852:Small Molecule Libraries / Q000032:analysis* / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D004273:DNA, Neoplasm; D006834:Hydrazines; D054852:Small Molecule Libraries; D019869:Phosphatidylinositol 3-Kinases; D066246:ErbB Receptors; D020928:Mitogen-Activated Protein Kinases