Enantioselective responses to a phosphorothioate analogue of lysophosphatidic acid with LPA3 receptor-selective agonist activity

  • J Med Chem. 2003 Dec 18;46(26):5575-8. doi: 10.1021/jm034207p.
Lian Qian  1 ,  Yong Xu ,  Yutaka Hasegawa ,  Junken Aoki ,  Gordon B Mills ,  Glenn D Prestwich
Affiliations
  • 1. Department of Medicinal Chemistry, The University of Utah, 419 Wakara Way, Suite 205, Salt Lake City, UT 84108, USA.
PMID: 14667211 DOI: 10.1021/jm034207p
Abstract

The metabolically stabilized LPA analogue, 1-oleoyl-2-O-methyl-rac-glycerophosphothioate (OMPT), is a potent agonist for the LPA(3) G-protein-coupled receptor. A new enantiospecific synthesis of both (2R)-OMPT and (2S)-OMPT is described. Calcium release assays in both LPA(3)-transfected insect Sf9 and rat hepatoma Rh7777 cells showed that (2S)-OMPT was 5- to 20-fold more active than (2R)-OMPT. Similar results were found for calcium release, MAPK and Akt activation, and IL-6 release in human OVCAR3 ovarian Cancer cells.

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