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Bioorg Med Chem Lett. 2007 Mar 15;17(6):1634-40. Epub 2007 Jan 13.

Synthesis and biological evaluation of phosphonate derivatives as autotaxin (ATX) inhibitors.

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  • 1Department of Chemistry, University of Virginia, McCormick Road, Charlottesville, VA 22904, USA. pc3n@virginia.edu

Abstract

Autotaxin (ATX) is an autocrine motility factor that promotes cancer cell invasion, cell migration, and angiogenesis. ATX, originally discovered as a nucleotide phosphodiesterase, is known now to be responsible for the lysophospholipid-preferring phospholipase D activity in plasma. As such, it catalyzes the production of lysophosphatidic acid (LPA) from lysophophatidylcholine (LPC). ATX is thus an attractive drug target; small molecular inhibitors might be efficacious in slowing the spread of cancers. With this study we have generated a series of beta-keto and beta-hydroxy phosphonate derivatives of LPA, some of which are potent ATX inhibitors.

PMID:
17257836
[PubMed - indexed for MEDLINE]
PMCID:
PMC4116752
Free PMC Article
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