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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
14
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pubmed:dateCreated |
2009-7-16
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pubmed:abstractText |
We report novel inhibitors of Gli1-mediated transcription as potential anticancer agents. Focused chemical libraries were designed and assessed for inhibition of functional cell-based Gli1-mediated transcription and selective toxicity toward cancer cells. The SAR was revealed, and the selectivity of the lead compounds' inhibition of Gli1-mediated transcription over that of Gli2 was determined. Compound 63 (NMDA298-1), which inhibited Gli1-mediated transcription in C3H10T1/2 cells with an IC(50) of 6.9 muM, showed 3-fold selectivity for inhibiting transcription mediated by Gli1 over that by Gli2. Cell-viability assays were performed to evaluate the chemical library in a normal cell line and a panel of cancer cell lines with or without up-regulated expression of the Gli1 gene. These compounds decreased the viability of several cancer cell lines but were less active in the noncancerous BJ-hTERT cells.
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pubmed:grant |
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pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/19545120-10725236,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19545120-11034076,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19545120-11731473,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19545120-12044012,
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http://linkedlifedata.com/resource/pubmed/commentcorrection/19545120-9916802
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Jul
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pubmed:issn |
1520-4804
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pubmed:author |
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pubmed:issnType |
Electronic
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pubmed:day |
23
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pubmed:volume |
52
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
4277-87
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pubmed:dateRevised |
2011-2-24
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pubmed:meshHeading |
pubmed-meshheading:19545120-Antineoplastic Agents,
pubmed-meshheading:19545120-Cell Line, Tumor,
pubmed-meshheading:19545120-Cell Survival,
pubmed-meshheading:19545120-Dose-Response Relationship, Drug,
pubmed-meshheading:19545120-Genes, Reporter,
pubmed-meshheading:19545120-Humans,
pubmed-meshheading:19545120-Inhibitory Concentration 50,
pubmed-meshheading:19545120-Neoplasms,
pubmed-meshheading:19545120-Oncogene Proteins,
pubmed-meshheading:19545120-Pyrazoles,
pubmed-meshheading:19545120-Structure-Activity Relationship,
pubmed-meshheading:19545120-Trans-Activators,
pubmed-meshheading:19545120-Transcription, Genetic,
pubmed-meshheading:19545120-Tyramine
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pubmed:year |
2009
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pubmed:articleTitle |
Structure-activity relationships and cancer-cell selective toxicity of novel inhibitors of glioma-associated oncogene homologue 1 (Gli1) mediated transcription.
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pubmed:affiliation |
St Jude Children's Research Hospital, Memphis, Tennessee 38105, USA.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't,
Research Support, N.I.H., Extramural
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