LPA and its analogs-attractive tools for elucidation of LPA biology and drug development

Kuniyuki Kano, Naoaki Arima, Mitsuru Ohgami, Junken Aoki

Research output: Contribution to journalReview articlepeer-review

38 Citations (Scopus)


Lysophosphatidic acid (LPA, 1- or 2-acyl-sn-glycerol 3-phosphate) is a simple phospholipid but displays an intriguing cell biology that is mediated via interactions with both G-protein-coupled seven transmembrane receptors (GPCRs) and nuclear hormone receptors. So far, seven GPCRs; (LPA1-5 and recently reported GPR87/LPA6 and P2Y5/LPA7) and a nuclear hormone receptors, PPARγ, have been identified. LPA is predominantly produced in blood and a plasma enzyme, autotaxin, is involved in its production. Recent gene manipulating studies of these proteins have shown that LPA is involved in both pathological and physiological states including brain development, neuropathy pain, implantation, protection against radiation-induced intestinal injury and blood vessel formation. In addition, lipids similar to LPA, such as sphingosine 1-phosphate (S1P) and 2-arachidonylglycerol (2-AG), share common cellular signaling pathways with LPA and are now considered as promising targets of human therapy including immunosuppressant and anti-obesity drugs. Thus, LPA is now one of the most attractive targets for prevention and treatment of various diseases. Receptor-selective antagonists and agonists as well as inhibitors of LPA producing enzymes are undoubtedly useful. Recognition of the ligand, LPA, by each receptor seems to be quite different, as LPA species with various fatty acids at either the sn-1 or sn-2 position of the hydroxy residue activate each receptor quite differently. In the last decade a series of LPA analogs in which the sn-1 or sn-2 hydroxy, acyl chain, glycerol and phosphate group are modified have been created and evaluated by several laboratories. Here we review recent advances in the development of LPA-receptor targeted compounds (agonists and antagonists) and anti-autotaxin inhibitors.

Original languageEnglish
Pages (from-to)2122-2131
Number of pages10
JournalCurrent Medicinal Chemistry
Issue number21
Publication statusPublished - 2008 Sep
Externally publishedYes


  • G protein-coupled receptor
  • LPA
  • LPA receptor
  • Lysophosphatidic acid
  • Nuclear hormone receptor
  • PPA Rγ

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Pharmacology
  • Drug Discovery
  • Organic Chemistry


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