Linked Life Data

19075574

Source:http://linkedlifedata.com/resource/pubmed/id/19075574

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
8
pubmed:dateCreated
2008-12-16
pubmed:abstractText
Autotaxin (ATX, autocrine motility factor, NPP2) has recently emerged as an attractive target for the development of anti-cancer chemotherapeutics. ATX contributes to the production of the bioactive lipid, lysophosphatidic acid (LPA), from lysophosphatidyl choline (LPC) in biological fluids including plasma, serum, and tumor cell effusates. LPA-stimulated cell proliferation, survival, motility and invasion have been demonstrated by numerous research groups. LPA receptors and ATX are upregulated in numerous cancer cell types and show expression patterns that correlate with tumor cell invasiveness. Despite considerable promise as an anti-cancer target, two complex challenges have slowed inhibitor discovery. The first of these challenges has been a lack of experimental details of the enzyme structure and its interactions with substrates or inhibitors. A second challenge has been a lack of structural diversity among initially reported inhibitors. Research reported in the last two years provides a foundation to begin addressing these challenges. Although an experimental structure of ATX is not among these recent developments, a crystal structure of the bacterial enzyme Xac. NPP is now available. This protein shares 35% identity with the central catalytic domain of ATX and provides an important starting point to begin understanding the structure of ATX. The structural diversity of known inhibitors has recently expanded to include not only phospholipid analogs, but also small molecules containing thiourea, diphenyldiazerenyl, anthracenedione and indole central cores. These two developments are essential tools for the discovery and optimization of ATX-targeted agents for evaluation as anti-cancer chemotherapeutic agents.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
1875-5992
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
8
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
917-23
pubmed:dateRevised
2011-11-17
pubmed:meshHeading
pubmed:year
2008
pubmed:articleTitle
Autotaxin inhibition: challenges and progress toward novel anti-cancer agents.
pubmed:affiliation
Department of Chemistry, and Computational Research on Materials Institute, The University of Memphis, Smith Chemistry Building, Room 213, Memphis, TN 38152, USA. aparrill@memphis.edu
pubmed:publicationType
Journal Article, Review