Linked Life Data

17249650

Source:http://linkedlifedata.com/resource/pubmed/id/17249650

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2007-2-15
pubmed:abstractText
Our laboratory recently reported the development of novel prodrug chemistry for the intracellular delivery of phosphotyrosine mimetics. This chemistry has now been adapted for the synthesis of a prodrug that delivers the nonhydrolyzable difluoromethylphosphonate moiety intracellularly. Activation of the prodrug generates a difluoromethylphosphonamidate anion that undergoes subsequent cyclization and hydrolysis with a t1/2 = 44 min. A highly potent and selective inhibitor of protein tyrosine phosphatase 1B (PTP1B) with a nanomolar Ki has been reported, but this bis(difluoromethylphosphonate) lacks potential utility due to its exceedingly low membrane permeability at physiological pH. A prodrug of this inhibitor has been synthesized and evaluated in a cell-based assay. The prodrug exhibits nanomolar PTP1B inhibitory activity in this assay, confirming the efficacy of intracellular phosphonate delivery using this prodrug approach.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
0022-2623
pubmed:author
pubmed:issnType
Print
pubmed:day
22
pubmed:volume
50
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
856-64
pubmed:dateRevised
2011-11-17
pubmed:meshHeading
pubmed-meshheading:17249650-Cell Line, Tumor, pubmed-meshheading:17249650-Cell Membrane Permeability, pubmed-meshheading:17249650-Dipeptides, pubmed-meshheading:17249650-Humans, pubmed-meshheading:17249650-Insulin, pubmed-meshheading:17249650-Magnetic Resonance Spectroscopy, pubmed-meshheading:17249650-Mitogen-Activated Protein Kinase 1, pubmed-meshheading:17249650-Mitogen-Activated Protein Kinase 3, pubmed-meshheading:17249650-Organophosphorus Compounds, pubmed-meshheading:17249650-Phosphorylation, pubmed-meshheading:17249650-Prodrugs, pubmed-meshheading:17249650-Protein Tyrosine Phosphatase, Non-Receptor Type 1, pubmed-meshheading:17249650-Protein Tyrosine Phosphatases, pubmed-meshheading:17249650-Receptor, Insulin, pubmed-meshheading:17249650-Signal Transduction, pubmed-meshheading:17249650-Structure-Activity Relationship
pubmed:year
2007
pubmed:articleTitle
Synthesis and cell-based activity of a potent and selective protein tyrosine phosphatase 1B inhibitor prodrug.
pubmed:affiliation
Department of Medicinal Chemistry and Molecular Pharmacology and the Cancer Center, Purdue University, West Lafayette, Indiana 47907, USA.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural