Linked Life Data

15033547

Source:http://linkedlifedata.com/resource/pubmed/id/15033547

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2004-3-22
pubmed:abstractText
Inherent or acquired resistance of tumor cells to anti-cancer drugs is a problem of major importance in chemotherapy. In addition to detailed research into the mechanisms of drug inactivation, attention has also been paid to the synthesis of new structures. Oracin is a promising cytostatic drug, which is presently in phase II of clinical trials. This investigation was designed to characterize the metabolic inactivation of oracin by carbonyl reduction to 11-dihydrooracin (DHO). We identified 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD 1) as the principal enzyme being responsible for oracin carbonyl reduction in human liver microsomes. The purified 11beta-HSD 1 catalyses this reaction in a stereospecific manner. Formation of (-)-DHO surpasses that of (+)-DHO by a factor of around four. Moreover, 11beta-HSD 1 exhibits enzyme cooperativity for the formation of both enantiomers (Hill coefficients of 2.26 +/- 0.20 and 1.84 +/- 0.29 for (-)-DHO and (+)-DHO, respectively). Comparing the differences in the stereospecificity and Hill coefficients between the microsomes and purified 11beta-HSD 1 could anticipate contribution of another microsomal enzyme. In case of oracin, this enzyme cooperativity may become important with respect to maximal plasma concentrations, and, by inhibition of 11beta-HSD 1, to enhance the chemotherapeutic efficacy of this anti-cancer drug.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
0300-483X
pubmed:author
pubmed:issnType
Print
pubmed:day
3
pubmed:volume
197
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
253-61
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
2004
pubmed:articleTitle
The novel anticancer drug oracin: different stereospecificity and cooperativity for carbonyl reduction by purified human liver 11beta-hydroxysteroid dehydrogenase type 1.
pubmed:affiliation
Department of Biochemical Sciences, Faculty of Pharmacy, Charles University, CZ-50005 Hradec Králové, Czech Republic.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't