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| pubmed-article:19907488 | lifeskim:mentions | umls-concept:C1235660 | lld:lifeskim |
| pubmed-article:19907488 | lifeskim:mentions | umls-concept:C1167128 | lld:lifeskim |
| pubmed-article:19907488 | lifeskim:mentions | umls-concept:C0021467 | lld:lifeskim |
| pubmed-article:19907488 | lifeskim:mentions | umls-concept:C0439851 | lld:lifeskim |
| pubmed-article:19907488 | lifeskim:mentions | umls-concept:C0021469 | lld:lifeskim |
| pubmed-article:19907488 | lifeskim:mentions | umls-concept:C1552596 | lld:lifeskim |
| pubmed-article:19907488 | lifeskim:mentions | umls-concept:C1947931 | lld:lifeskim |
| pubmed-article:19907488 | pubmed:issue | 7270 | lld:pubmed |
| pubmed-article:19907488 | pubmed:dateCreated | 2009-11-12 | lld:pubmed |
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| pubmed-article:19907488 | pubmed:databankReference | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:19907488 | pubmed:abstractText | Direct inhibition of transcription factor complexes remains a central challenge in the discipline of ligand discovery. In general, these proteins lack surface involutions suitable for high-affinity binding by small molecules. Here we report the design of synthetic, cell-permeable, stabilized alpha-helical peptides that target a critical protein-protein interface in the NOTCH transactivation complex. We demonstrate that direct, high-affinity binding of the hydrocarbon-stapled peptide SAHM1 prevents assembly of the active transcriptional complex. Inappropriate NOTCH activation is directly implicated in the pathogenesis of several disease states, including T-cell acute lymphoblastic leukaemia (T-ALL). The treatment of leukaemic cells with SAHM1 results in genome-wide suppression of NOTCH-activated genes. Direct antagonism of the NOTCH transcriptional program causes potent, NOTCH-specific anti-proliferative effects in cultured cells and in a mouse model of NOTCH1-driven T-ALL. | lld:pubmed |
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| pubmed-article:19907488 | pubmed:language | eng | lld:pubmed |
| pubmed-article:19907488 | pubmed:journal | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:19907488 | pubmed:citationSubset | IM | lld:pubmed |
| pubmed-article:19907488 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
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| pubmed-article:19907488 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
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| pubmed-article:19907488 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
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| pubmed-article:19907488 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:19907488 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
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| pubmed-article:19907488 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:19907488 | pubmed:status | MEDLINE | lld:pubmed |
| pubmed-article:19907488 | pubmed:month | Nov | lld:pubmed |
| pubmed-article:19907488 | pubmed:issn | 1476-4687 | lld:pubmed |
| pubmed-article:19907488 | pubmed:author | pubmed-author:BlacklowSteph... | lld:pubmed |
| pubmed-article:19907488 | pubmed:author | pubmed-author:GillilandD... | lld:pubmed |
| pubmed-article:19907488 | pubmed:author | pubmed-author:AsterJon CJC | lld:pubmed |
| pubmed-article:19907488 | pubmed:author | pubmed-author:VerdineGregor... | lld:pubmed |
| pubmed-article:19907488 | pubmed:author | pubmed-author:KungAndrew... | lld:pubmed |
| pubmed-article:19907488 | pubmed:author | pubmed-author:Del... | lld:pubmed |
| pubmed-article:19907488 | pubmed:author | pubmed-author:BradnerJames... | lld:pubmed |
| pubmed-article:19907488 | pubmed:author | pubmed-author:MoelleringRay... | lld:pubmed |
| pubmed-article:19907488 | pubmed:author | pubmed-author:DavisTina NTN | lld:pubmed |
| pubmed-article:19907488 | pubmed:author | pubmed-author:CornejoMelani... | lld:pubmed |
| pubmed-article:19907488 | pubmed:issnType | Electronic | lld:pubmed |
| pubmed-article:19907488 | pubmed:day | 12 | lld:pubmed |
| pubmed-article:19907488 | pubmed:volume | 462 | lld:pubmed |
| pubmed-article:19907488 | pubmed:owner | NLM | lld:pubmed |
| pubmed-article:19907488 | pubmed:authorsComplete | Y | lld:pubmed |
| pubmed-article:19907488 | pubmed:pagination | 182-8 | lld:pubmed |
| pubmed-article:19907488 | pubmed:dateRevised | 2011-3-29 | lld:pubmed |
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| pubmed-article:19907488 | pubmed:year | 2009 | lld:pubmed |
| pubmed-article:19907488 | pubmed:articleTitle | Direct inhibition of the NOTCH transcription factor complex. | lld:pubmed |
| pubmed-article:19907488 | pubmed:affiliation | Department of Chemistry & Chemical Biology, Harvard University, Cambridge, Massachusetts 02138, USA. | lld:pubmed |
| pubmed-article:19907488 | pubmed:publicationType | Journal Article | lld:pubmed |
| pubmed-article:19907488 | pubmed:publicationType | Research Support, Non-U.S. Gov't | lld:pubmed |
| pubmed-article:19907488 | pubmed:publicationType | Research Support, N.I.H., Extramural | lld:pubmed |
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