Molecular basis for lysophosphatidic acid receptor antagonist selectivity

Biochim Biophys Acta. 2002 May 23;1582(1-3):309-17. doi: 10.1016/s1388-1981(02)00185-3.


Recent characterization of lysophosphatidic acid (LPA) receptors has made possible studies elucidating the structure-activity relationships (SAR) for agonist activity at individual receptors. Additionally, the availability of these receptors has allowed the identification of antagonists of LPA-induced effects. Two receptor-subtype selective LPA receptor antagonists, one selective for the LPA1/EDG2 receptor (a benzyl-4-oxybenzyl N-acyl ethanolamide phosphate, NAEPA, derivative) and the other selective for the LPA3/EDG7 receptor (diacylglycerol pyrophosphate, DGPP, 8:0), have recently been reported. The receptor SAR for both agonists and antagonists are reviewed, and the molecular basis for the difference between agonism and antagonism as well as for receptor-subtype antagonist selectivity identified by molecular modeling is described. The implications of the newly available receptor-subtype selective antagonists are also discussed.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Binding Sites
  • Humans
  • Ligands
  • Models, Molecular
  • Molecular Sequence Data
  • Phospholipids / chemistry
  • Phospholipids / pharmacology*
  • Protein Conformation
  • Receptors, Cell Surface / antagonists & inhibitors*
  • Receptors, Cell Surface / chemistry
  • Receptors, Cell Surface / drug effects
  • Receptors, G-Protein-Coupled*
  • Receptors, Lysophosphatidic Acid
  • Sequence Alignment
  • Sequence Homology, Amino Acid


  • Ligands
  • Phospholipids
  • Receptors, Cell Surface
  • Receptors, G-Protein-Coupled
  • Receptors, Lysophosphatidic Acid