Linked Life Data

18768317

Source:http://linkedlifedata.com/resource/pubmed/id/18768317

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
18
pubmed:dateCreated
2008-9-15
pubmed:abstractText
The Stat3 SH2 domain is essential for its activation, and development of a potent SH2 inhibitor will be therapeutically valuable in treating cancers with constant Stat3 activation. We report here the identification of the catechol (1,2-dihydroxybenzene) structural moiety by virtual screening as a Stat3 SH2 inhibitor. The catechol compound docked to the Stat3 SH2 domain in computer modeling forms hydrogen bonds with the conserved pTyr-interacting amino acids. In the biochemical assay, a catechol-containing compound, but not the hydroxyl group-acetalized analogue, was able to inhibit Stat3 DNA-binding activity. Furthermore, the catechol compound was demonstrated to compete with pTyr peptides in binding to the Stat3 SH2 domain, suggesting that the catechol moiety is a pTyr bioisostere and may potentially be used for designing cell-permeable SH2 inhibitors. In our preliminary effort, we also demonstrated that the potency of catechol compound as Stat3 SH2 inhibitors could be improved by modifying the non-catechol part of the compound structure.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
1464-3405
pubmed:author
pubmed:issnType
Electronic
pubmed:day
15
pubmed:volume
18
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
4988-92
pubmed:meshHeading
pubmed:year
2008
pubmed:articleTitle
Discovery of the catechol structural moiety as a Stat3 SH2 domain inhibitor by virtual screening.
pubmed:affiliation
Oncology, Wyeth Pharmaceuticals, 401 N. Middletown Road, Pearl River, NY 10965, USA. haow@wyeth.com
pubmed:publicationType
Journal Article