Linked Life Data

21443218

Source:http://linkedlifedata.com/resource/pubmed/id/21443218

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
8
pubmed:dateCreated
2011-4-21
pubmed:abstractText
To optimize the antitumor activity of oncrasin-1, a small molecule RNA polymerase II inhibitor, we evaluated 69 oncrasin-1 analogues for their cytotoxic activity against normal human epithelial cells and K-Ras mutant tumor cells. About 40 of those compounds were as potent as or more potent than oncrasin-1 in tumor cells and had a minimal cytotoxic effect on normal cells. Structure-activity relationship analysis revealed that most of the active compounds contained either a hydroxymethyl group or an aldehyde group as a substitute at the 3-position of the indole. Both electron-donating and electron-withdrawing groups in the benzene ring were well tolerated. The hydroxymethyl compounds ranged from equipotent with to 100 times as potent as the corresponding aldehyde compounds. We tested three active analogues' effect on RNA polymerase phosphorylation and found that they all inhibited phosphorylation of the C-terminal domain of RNA polymerase II, suggesting that the active compounds might act through the same mechanisms as oncrasin-1.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
1520-4804
pubmed:author
pubmed:issnType
Electronic
pubmed:day
28
pubmed:volume
54
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2668-79
pubmed:dateRevised
2011-10-25
pubmed:meshHeading
pubmed:year
2011
pubmed:articleTitle
Analogues and derivatives of oncrasin-1, a novel inhibitor of the C-terminal domain of RNA polymerase II and their antitumor activities.
pubmed:affiliation
Department of Thoracic and Cardiovascular Surgery, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, United States.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural