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Autotaxin inhibitors: a perspective on initial medicinal chemistry efforts.

Abstract
The lysophospholipase D enzyme, autotaxin (ATX), has been linked to numerous human diseases including cancer, neurophatic pain, obesity and Alzheimer's disease. Although the ATX protein was initially purified and characterized in 1992, a link to bioactive lipid metabolism was not made until 2002. In the past decade, metal chelators, lysophospholipid product analogs, and more recently, small non-lipid inhibitors of the enzyme were successfully identified. The majority of these inhibitors have been characterized using recombinant purified ATX in vitro, with very few examples studied in more complex systems. Translation of ATX inhibitors from the hands of medicinal chemists to clinical use will require substantially expanded characterization of ATX inhibitors in vivo.
AuthorsAbby L Parrill, Daniel L Baker
JournalExpert opinion on therapeutic patents (Expert Opin Ther Pat) Vol. 20 Issue 12 Pg. 1619-25 (Dec 2010) ISSN: 1744-7674 [Electronic] England
PMID21047298 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
Chemical References
  • Antineoplastic Agents
  • Multienzyme Complexes
  • Phosphoric Diester Hydrolases
  • Phosphodiesterase I
  • alkylglycerophosphoethanolamine phosphodiesterase
  • Pyrophosphatases
Topics
  • Animals
  • Antineoplastic Agents (pharmacology)
  • Drug Delivery Systems
  • Humans
  • Lipid Metabolism
  • Multienzyme Complexes (antagonists & inhibitors)
  • Neoplasms (drug therapy, physiopathology)
  • Phosphodiesterase I (antagonists & inhibitors)
  • Phosphoric Diester Hydrolases
  • Pyrophosphatases (antagonists & inhibitors)

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