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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.


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.

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