Linked Life Data

10579854

Source:http://linkedlifedata.com/resource/pubmed/id/10579854

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
23
pubmed:dateCreated
1999-12-17
pubmed:abstractText
The pharmacologic efficacy of the promising antitumor agent paclitaxel (Taxol) may be potentially enhanced through derivatization of the drug to a water-soluble tumor-recognizing conjugate. This work reports the design and synthesis of the first tumor-directed derivative of paclitaxel. A 7-amino acid synthetic peptide, BBN[7-13], which binds to the cell surface bombesin/gastrin-releasing peptide (BBN/GRP) receptor, was conjugated to the paclitaxel-2'-hydroxy function by a heterobifunctional poly(ethylene glycol) linker. The resulting conjugate, designated PTXPEGBBN[7-13], was soluble to the upper limit of tested concentrations (250 mg/mL). The conjugate completely retained the receptor binding properties of the attached peptide as compared with those of the unconjugated BBN[7-13]. In experiments with NCI-H1299 human nonsmall cell lung cancer cells, the cytotoxicity of the PTXPEGBBN[7-13] conjugate at a 15 nM dose was enhanced by a factor of 17.3 for 24 h and 10 for 96 h exposure times, relative to paclitaxel. The IC(50) of the conjugate, tested against the same cell line, was lower than the free drug by a factor of 2.5 for both 24 h and 96 h exposures. These results describe, for the first time, the design and synthesis of a soluble tumor-directed paclitaxel prodrug which may establish a new mode for the utilization of this drug in cancer therapy.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
0022-2623
pubmed:author
pubmed:issnType
Print
pubmed:day
18
pubmed:volume
42
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
4919-24
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
1999
pubmed:articleTitle
Paclitaxel derivatives for targeted therapy of cancer: toward the development of smart taxanes.
pubmed:affiliation
Departments of Radiation Oncology and Medicine, and The Comprehensive Cancer Center, University of Alabama at Birmingham, 35294, USA. safavy@uab.edu
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't