Linked Life Data

15787967

Source:http://linkedlifedata.com/resource/pubmed/id/15787967

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2005-3-24
pubmed:abstractText
A novel type of water-soluble prodrugs of cyclosporine A (CsA) is described, featuring a modular system of an enzyme-cleavable group, a solubilizing moiety and a chemodegradable spacer attached to the hydroxyl function of (4R)-4-[(E)-2-butenyl]-4-,N-dimethyl-l-threonine (MeBmt)-1 of CsA. The chemical synthesis of these double prodrugs proceeds in high yield and purity and allows for a systematic study of the influence of the structural parameters upon physicochemical and pharmacological properties. The evaluation of the chemical and enzymatic stability results in differential values of the conversion rates (minutes to several hours) in support of an enzyme-triggered release of the parent drug as the rate-limiting step. In vitro studies show that the designed prodrug systems can be regarded as soft prodrugs in being devoid of cyclophiline A (CypA) binding and that complete conversion to the parent drug occurs in whole rat blood, setting the stage for therapeutic use.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
1397-002X
pubmed:author
pubmed:issnType
Print
pubmed:volume
65
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
364-74
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
2005
pubmed:articleTitle
Water-soluble prodrugs of cyclosporine A with tailored conversion rates.
pubmed:affiliation
Ecole Polytechnique Fédérale de Lausanne (EPFL), Institute of Chemical Sciences and Engineering (ISIC), Lausanne, Switzerland.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't