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rdf:type |
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lifeskim:mentions |
umls-concept:C0021467,
umls-concept:C0021469,
umls-concept:C0033684,
umls-concept:C0041485,
umls-concept:C0080298,
umls-concept:C0162638,
umls-concept:C0205263,
umls-concept:C0334227,
umls-concept:C0441655,
umls-concept:C0567416,
umls-concept:C0700307,
umls-concept:C1280500,
umls-concept:C1334043,
umls-concept:C1334896,
umls-concept:C1335073,
umls-concept:C1512773,
umls-concept:C2697616
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pubmed:issue |
18
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pubmed:dateCreated |
2008-9-19
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pubmed:abstractText |
(E)-4-[3-(1-Adamantyl)-4'-hydroxyphenyl]-3-chlorocinnamic acid (3-Cl-AHPC) induces the cell-cycle arrest and apoptosis of leukemia and cancer cells. Studies demonstrated that 3-Cl-AHPC bound to the atypical orphan nuclear receptor small heterodimer partner (SHP). Although missing a DNA-binding domain, SHP heterodimerizes with the ligand-binding domains of other nuclear receptors to repress their abilities to induce or inhibit gene expression. 3-Cl-AHPC analogues having the 1-adamantyl and phenolic hydroxyl pharmacophoric elements replaced with isosteric groups were designed, synthesized, and evaluated for their inhibition of proliferation and induction of human cancer cell apoptosis. Structure-anticancer activity relationship studies indicated the importance of both groups to apoptotic activity. Docking of 3-Cl-AHPC and its analogues to an SHP computational model that was based on the crystal structure of ultraspiracle complexed with 1-stearoyl-2-palmitoylglycero-3-phosphoethanolamine suggested why these 3-Cl-AHPC groups could influence SHP activity. Inhibitory activity against Src homology 2 domain-containing protein tyrosine phosphatase 2 (Shp-2) was also assessed. The most active Shp-2 inhibitor was found to be the 3'-(3,3-dimethylbutynyl) analogue of 3-Cl-AHPC.
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pubmed:grant |
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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 |
Sep
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pubmed:issn |
1520-4804
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pubmed:author |
pubmed-author:BhuiyanMohammadM,
pubmed-author:ChaoWan-RuWR,
pubmed-author:DawsonMarcia IMI,
pubmed-author:FarhanaLuluL,
pubmed-author:FengGen-ShengGS,
pubmed-author:FontanaJoseph AJA,
pubmed-author:HanYoung-HoonYH,
pubmed-author:HobbsPeter DPD,
pubmed-author:JiangTaoT,
pubmed-author:JongLingL,
pubmed-author:MacchiaruloAntonioA,
pubmed-author:NutiRobertoR,
pubmed-author:PangYuhongY,
pubmed-author:PatelBhaumikB,
pubmed-author:PellicciariRobertoR,
pubmed-author:SuYingY,
pubmed-author:TautzLutzL,
pubmed-author:WalehNahidN,
pubmed-author:XiaZebinZ,
pubmed-author:XueLi PingLP,
pubmed-author:YeMaoM,
pubmed-author:ZhangXiao-KunXK
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pubmed:issnType |
Electronic
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pubmed:day |
25
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pubmed:volume |
51
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
5650-62
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pubmed:dateRevised |
2010-12-3
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pubmed:meshHeading |
pubmed-meshheading:18759424-Adamantane,
pubmed-meshheading:18759424-Antineoplastic Agents,
pubmed-meshheading:18759424-Apoptosis,
pubmed-meshheading:18759424-Cell Division,
pubmed-meshheading:18759424-Cell Line, Tumor,
pubmed-meshheading:18759424-Cinnamates,
pubmed-meshheading:18759424-Dimerization,
pubmed-meshheading:18759424-Enzyme Inhibitors,
pubmed-meshheading:18759424-Humans,
pubmed-meshheading:18759424-Models, Molecular,
pubmed-meshheading:18759424-Neoplasms,
pubmed-meshheading:18759424-Protein Tyrosine Phosphatase, Non-Receptor Type 11
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pubmed:year |
2008
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pubmed:articleTitle |
Adamantyl-substituted retinoid-derived molecules that interact with the orphan nuclear receptor small heterodimer partner: effects of replacing the 1-adamantyl or hydroxyl group on inhibition of cancer cell growth, induction of cancer cell apoptosis, and inhibition of SRC homology 2 domain-containing protein tyrosine phosphatase-2 activity.
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pubmed:affiliation |
Cancer Center and Inflammatory and Infectious Disease Center, Burnham Institute for Medical Research, La Jolla, California 92037, USA. mdawson@burnham.org
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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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