Linked Life Data

20236786

Source:http://linkedlifedata.com/resource/pubmed/id/20236786

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
2010-4-5
pubmed:abstractText
The effect of acid treatment of cyclopamine, a natural antagonist of the hedgehog (Hh) signaling pathway and a potential anti-cancer drug, has been studied. Previous reports have shown that under acidic conditions, as in the stomach, cyclopamine is less effective. Also, it has been stated that cyclopamine converts to veratramine, which has side effects such as hemolysis. In this study, we examined in detail the influence of acidification on structure and activity of cyclopamine. We found that of acidified cyclopamine converts to two previously unreported isomers, which we have called cyclopamine (S) and cyclopamine (X). These have likely gone undetected because cyclopamine is often analyzed with fast and hence lower resolving chromatographic methods. Compared to natural cyclopamine, these cyclopamine isomers have a significantly reduced effect on the ciliary transport of the Hh receptor smoothened, and reduced inhibition on the Hedgehog signaling pathway. The side effects of these isomers are unknown. Our findings can partly explain a reduced efficiency of cyclopamine in a gastric environment, and may help with the rational design of more pH independent cyclopamine analogues.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
1873-264X
pubmed:author
pubmed:copyrightInfo
2010 Elsevier B.V. All rights reserved.
pubmed:issnType
Electronic
pubmed:day
5
pubmed:volume
52
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
707-13
pubmed:meshHeading
pubmed:year
2010
pubmed:articleTitle
Hedgehog antagonist cyclopamine isomerizes to less potent forms when acidified.
pubmed:affiliation
Department of Chemistry, University of Oslo, P.O. Box 1033, Blindern, NO-0315, Oslo, Norway. stevenw@kjemi.uio.no
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't