| pubmed-article:21216604 | rdf:type | pubmed:Citation | lld:pubmed |
| pubmed-article:21216604 | lifeskim:mentions | umls-concept:C0020205 | lld:lifeskim |
| pubmed-article:21216604 | lifeskim:mentions | umls-concept:C0253050 | lld:lifeskim |
| pubmed-article:21216604 | lifeskim:mentions | umls-concept:C2936235 | lld:lifeskim |
| pubmed-article:21216604 | lifeskim:mentions | umls-concept:C0220781 | lld:lifeskim |
| pubmed-article:21216604 | lifeskim:mentions | umls-concept:C1883254 | lld:lifeskim |
| pubmed-article:21216604 | lifeskim:mentions | umls-concept:C1533691 | lld:lifeskim |
| pubmed-article:21216604 | lifeskim:mentions | umls-concept:C0243077 | lld:lifeskim |
| pubmed-article:21216604 | lifeskim:mentions | umls-concept:C0679622 | lld:lifeskim |
| pubmed-article:21216604 | lifeskim:mentions | umls-concept:C1707689 | lld:lifeskim |
| pubmed-article:21216604 | lifeskim:mentions | umls-concept:C1880022 | lld:lifeskim |
| pubmed-article:21216604 | lifeskim:mentions | umls-concept:C0205314 | lld:lifeskim |
| pubmed-article:21216604 | pubmed:issue | 5 | lld:pubmed |
| pubmed-article:21216604 | pubmed:dateCreated | 2011-3-1 | lld:pubmed |
| pubmed-article:21216604 | pubmed:abstractText | Aberrant activation of oncogenic signal transducer and activator of transcription 3 (STAT3) protein signaling pathways has been extensively implicated in human cancers. Given STAT3's prominent dysregulatory role in malignant transformation and tumorigenesis, there has been a significant effort to discover STAT3-specific inhibitors as chemical probes for defining the aberrant STAT3-mediated molecular events that support the malignant phenotype. To identify novel, STAT3-selective inhibitors suitable for interrogating STAT3 signaling in tumor cells, we explored the design of hybrid molecules by conjugating a known STAT3 inhibitory peptidomimetic, ISS610 to the high-affinity STAT3-binding peptide motif derived from the ILR/gp-130. Several hybrid molecules were examined in in vitro biophysical and biochemical studies for inhibitory potency against STAT3. Lead inhibitor 14aa was shown to strongly bind to STAT3 (K(D)=900 nM), disrupt STAT3:phosphopeptide complexes (K(i)=5 ?M) and suppress STAT3 activity in in vitro DNA binding activity/electrophoretic mobility shift assay (EMSA). Moreover, lead STAT3 inhibitor 14aa induced a time-dependent inhibition of constitutive STAT3 activation in v-Src transformed mouse fibroblasts (NIH3T3/v-Src), with 80% suppression of constitutively-active STAT3 at 6h following treatment of NIH3T3/v-Src. However, STAT3 activity recovered at 24h after treatment of cells, suggesting potential degradation of the compound. Results further showed a suppression of aberrant STAT3 activity in NIH3T3/v-Src by the treatment with compound 14aa-OH, which is the non-pTyr version of compound 14aa. The effect of compounds 14aa and 14aa-OH are accompanied by a moderate loss of cell viability. | lld:pubmed |
| pubmed-article:21216604 | pubmed:grant | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:21216604 | pubmed:grant | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:21216604 | pubmed:grant | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:21216604 | pubmed:language | eng | lld:pubmed |
| pubmed-article:21216604 | pubmed:journal | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:21216604 | pubmed:citationSubset | IM | lld:pubmed |
| pubmed-article:21216604 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:21216604 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:21216604 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:21216604 | pubmed:status | MEDLINE | lld:pubmed |
| pubmed-article:21216604 | pubmed:month | Mar | lld:pubmed |
| pubmed-article:21216604 | pubmed:issn | 1464-3391 | lld:pubmed |
| pubmed-article:21216604 | pubmed:author | pubmed-author:HarhJ YJY | lld:pubmed |
| pubmed-article:21216604 | pubmed:author | pubmed-author:ZhaoWeiW | lld:pubmed |
| pubmed-article:21216604 | pubmed:author | pubmed-author:SchimmerAaron... | lld:pubmed |
| pubmed-article:21216604 | pubmed:author | pubmed-author:ZhangXiaoleiX | lld:pubmed |
| pubmed-article:21216604 | pubmed:author | pubmed-author:TurksonJamesJ | lld:pubmed |
| pubmed-article:21216604 | pubmed:author | pubmed-author:PeibinYueY | lld:pubmed |
| pubmed-article:21216604 | pubmed:author | pubmed-author:SukhaiMahadeo... | lld:pubmed |
| pubmed-article:21216604 | pubmed:author | pubmed-author:FletcherSteve... | lld:pubmed |
| pubmed-article:21216604 | pubmed:author | pubmed-author:GunningPatric... | lld:pubmed |
| pubmed-article:21216604 | pubmed:author | pubmed-author:SharmeenSumai... | lld:pubmed |
| pubmed-article:21216604 | pubmed:author | pubmed-author:ShahaniVijay... | lld:pubmed |
| pubmed-article:21216604 | pubmed:author | pubmed-author:LuuDiana PDP | lld:pubmed |
| pubmed-article:21216604 | pubmed:copyrightInfo | Copyright © 2010 Elsevier Ltd. All rights reserved. | lld:pubmed |
| pubmed-article:21216604 | pubmed:issnType | Electronic | lld:pubmed |
| pubmed-article:21216604 | pubmed:day | 1 | lld:pubmed |
| pubmed-article:21216604 | pubmed:volume | 19 | lld:pubmed |
| pubmed-article:21216604 | pubmed:owner | NLM | lld:pubmed |
| pubmed-article:21216604 | pubmed:authorsComplete | Y | lld:pubmed |
| pubmed-article:21216604 | pubmed:pagination | 1823-38 | lld:pubmed |
| pubmed-article:21216604 | pubmed:dateRevised | 2011-8-9 | lld:pubmed |
| pubmed-article:21216604 | pubmed:meshHeading | pubmed-meshheading:21216604... | lld:pubmed |
| pubmed-article:21216604 | pubmed:meshHeading | pubmed-meshheading:21216604... | lld:pubmed |
| pubmed-article:21216604 | pubmed:meshHeading | pubmed-meshheading:21216604... | lld:pubmed |
| pubmed-article:21216604 | pubmed:meshHeading | pubmed-meshheading:21216604... | lld:pubmed |
| pubmed-article:21216604 | pubmed:meshHeading | pubmed-meshheading:21216604... | lld:pubmed |
| pubmed-article:21216604 | pubmed:meshHeading | pubmed-meshheading:21216604... | lld:pubmed |
| pubmed-article:21216604 | pubmed:meshHeading | pubmed-meshheading:21216604... | lld:pubmed |
| pubmed-article:21216604 | pubmed:meshHeading | pubmed-meshheading:21216604... | lld:pubmed |
| pubmed-article:21216604 | pubmed:meshHeading | pubmed-meshheading:21216604... | lld:pubmed |
| pubmed-article:21216604 | pubmed:year | 2011 | lld:pubmed |
| pubmed-article:21216604 | pubmed:articleTitle | Design, synthesis, and in vitro characterization of novel hybrid peptidomimetic inhibitors of STAT3 protein. | lld:pubmed |
| pubmed-article:21216604 | pubmed:affiliation | Department of Chemistry, University of Toronto, Mississauga, ON, Canada. | lld:pubmed |
| pubmed-article:21216604 | pubmed:publicationType | Journal Article | lld:pubmed |
| pubmed-article:21216604 | pubmed:publicationType | Research Support, Non-U.S. Gov't | lld:pubmed |
| pubmed-article:21216604 | pubmed:publicationType | Research Support, N.I.H., Extramural | lld:pubmed |
| http://linkedlifedata.com/r... | http://linkedlifedata.com/r... | pubmed-article:21216604 | lld:chembl |
