title: Synthesis and biological evaluation of phosphonate derivatives as autotaxin (ATX) inhibitors.
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.
authors.affiliation: Department of Chemistry, University of Virginia, McCormick Road, Charlottesville, VA 22904, USA. pc3n@virginia.edu
authors.forename: Peng
authors.initials: P
authors.lastname: Cui
authors.forename: Jose L
authors.initials: JL
authors.lastname: Tomsig
authors.forename: William F
authors.initials: WF
authors.lastname: McCalmont
authors.forename: Sangderk
authors.initials: S
authors.lastname: Lee
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Becker
authors.forename: Kevin R
authors.initials: KR
authors.lastname: Lynch
authors.forename: Timothy L
authors.initials: TL
authors.lastname: Macdonald
mesh_terms: D006868:Hydrolysis; D007202:Indicators and Reagents; D008246:Lysophospholipids / Q000138:chemical synthesis / Q000737:chemistry; D009097:Multienzyme Complexes / Q000037:antagonists & inhibitors*; D063065:Organophosphonates / Q000138:chemical synthesis* / Q000494:pharmacology*; D043264:Phosphodiesterase I / Q000037:antagonists & inhibitors*; D010727:Phosphoric Diester Hydrolases; D011755:Pyrophosphatases / Q000037:antagonists & inhibitors*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D000099189:Lysophospholipase D
chemical_list: D007202:Indicators and Reagents; D008246:Lysophospholipids; D009097:Multienzyme Complexes; D063065:Organophosphonates; D043264:Phosphodiesterase I; D010727:Phosphoric Diester Hydrolases; D011755:Pyrophosphatases; D000099189:Lysophospholipase D; C032881:lysophosphatidic acid