Linked Life Data

10381366

Source:http://linkedlifedata.com/resource/pubmed/id/10381366

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
1999-7-29
pubmed:abstractText
7-Ethyl-10-hydroxycamptothecin (SN-38) is a very promising anticancer drug used for the treatment of metastatic colonrectal cancer. SN-38 is the active metabolite of irinotecan, a semisynthetic anticancer drug derived from 20(S)camptothecin. In this study, we examined the potential for each of the UGT1-encoded isoforms (UGT1A1 and UGT1A3 through UGT1A10) to glucuronidate SN-38. The amount of specific protein for each isoform was determined by Western blot analysis. Although UGT1A1 was previously shown to metabolize this drug, the results of this study show that UGT1A7 glucuronidates this chemical at a 9- to 21-fold higher level at pH 6. 4 and pH 7.6, respectively, than that by UGT1A1. The activity of UGT1A7 is from 8.4- to 19-fold higher at pH 6.4 and 12- to 40-fold higher at pH 7.6 than that by the other 7 UGT1 encoded isoforms. UGT1A7 glucuronidates SN-38 with an apparent Km of 5 microM. Hence, the distribution of this isoform in the gastrointestinal tract has the potential to impact the effectiveness of this chemotherapeutic agent.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
0006-291X
pubmed:author
pubmed:copyrightInfo
Copyright 1999 Academic Press.
pubmed:issnType
Print
pubmed:day
24
pubmed:volume
260
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
199-202
pubmed:dateRevised
2007-9-25
pubmed:meshHeading
pubmed:year
1999
pubmed:articleTitle
Glucuronidation of 7-ethyl-10-hydroxycamptothecin (SN-38) by the human UDP-glucuronosyltransferases encoded at the UGT1 locus.
pubmed:affiliation
Heritable Disorders Branch, NICHD, Bethesda, Maryland, 20892, USA.
pubmed:publicationType
Journal Article