Linked Life Data

20621484

Source:http://linkedlifedata.com/resource/pubmed/id/20621484

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
15
pubmed:dateCreated
2010-7-23
pubmed:abstractText
Screening of the NCI Diversity Set-1 identified PI-083 (NSC-45382) a proteasome inhibitor selective for cancer over normal cells. Focused libraries of novel compounds based on PI-083 chloronaphthoquinone and sulfonamide moieties were synthesized to gain a better understanding of the structure-activity relationship responsible for chymotrypsin-like proteasome inhibitory activity. This led to the demonstration that the chloronaphthoquinone and the sulfonamide moieties are critical for inhibitory activity. The pyridyl group in PI-083 can be replaced with other heterocyclic groups without significant loss of activity. Molecular modeling studies were also performed to explore the detailed interactions of PI-083 and its derivatives with the beta5 and beta6 subunits of the 20S proteasome. The refined model showed an H-bond interaction between the Asp-114 and the sulfonamide moiety of the PI-083 in the beta6 subunit.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
1464-3391
pubmed:author
pubmed:copyrightInfo
Copyright (c) 2010 Elsevier Ltd. All rights reserved.
pubmed:issnType
Electronic
pubmed:day
1
pubmed:volume
18
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
5576-92
pubmed:meshHeading
pubmed:year
2010
pubmed:articleTitle
Synthesis and biological evaluation of naphthoquinone analogs as a novel class of proteasome inhibitors.
pubmed:affiliation
Drug Discovery Department, Moffitt Cancer Center, 12901 Magnolia Drive, Tampa, FL 33612, USA. Harshani.Lawrence@moffitt.org
pubmed:publicationType
Journal Article, Research Support, N.I.H., Extramural