Linked Life Data

16854074

Source:http://linkedlifedata.com/resource/pubmed/id/16854074

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
15
pubmed:dateCreated
2006-7-20
pubmed:abstractText
Previously, we demonstrated that the peroxisome proliferator-activated receptor gamma (PPARgamma) agonist troglitazone mediated the repression of cyclin D1 in MCF-7 breast cancer cells by facilitating proteasome-facilitated proteolysis. This PPARgamma-independent mechanism provided a molecular basis for using troglitazone as scaffold to develop a novel class of cyclin D1-ablative agents. The proof of principle of this premise is provided by Delta2TG, in which the introduction of a double bond adjacent to the thiazolidinedione ring abrogated the PPARgamma activity while retaining the activity in cyclin D1 repression. Structural optimization of Delta2TG led to STG28 [(S)-5-(4-{[6-(allyloxy)-2,5,7,8-tetramethylchroman-2-yl]methoxy}-3-methoxybenzylidene)thiazolidine-2,4-dione], which exhibited low micromolar potency in ablating cyclin D1 and inhibiting MCF-7 cell proliferation. It is noteworthy that STG28 mediated the proteasomal degradation of cyclin D1 with a high degree of specificity. Exposure to STG28 did not cause any appreciable change in the expression levels of a series of other cyclins and CDK-dependent kinases. In light of the pivotal role of cyclin D1 in promoting tumorigenesis and drug resistance, this novel cyclin D1-ablating agent may have therapeutic relevance in cancer therapy.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
0022-2623
pubmed:author
pubmed:issnType
Print
pubmed:day
27
pubmed:volume
49
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
4684-9
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
2006
pubmed:articleTitle
Development of small-molecule cyclin D1-ablative agents.
pubmed:affiliation
Division of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, 336 Parks Hall, The Ohio State University, 500 West 12th Avenue, Columbus, Ohio 43210, USA.
pubmed:publicationType
Journal Article, Research Support, N.I.H., Extramural