Potent S1P receptor agonists replicate the pharmacologic actions of the novel immune modulator FTY720

Bioorg Med Chem Lett. 2004 Jun 21;14(12):3351-5. doi: 10.1016/j.bmcl.2004.02.106.

Abstract

Alteration in lymphocyte trafficking and prevention of graft rejection in rodents observed on exposure to FTY720 (1) or its corresponding phosphate ester 2 can be induced by the systemic administration of potent sphingosine-1-phosphate receptor agonists exemplified by 19. The similar S1P receptor profiles of 2 and 19 coupled with their comparable potency in vivo supports a connection between S1P receptor agonism and immunosuppressive efficacy.

MeSH terms

  • Animals
  • CHO Cells
  • Cricetinae
  • Fingolimod Hydrochloride
  • Humans
  • Immunologic Factors / administration & dosage*
  • Immunologic Factors / chemistry*
  • Immunologic Factors / metabolism
  • Immunosuppressive Agents / administration & dosage
  • Immunosuppressive Agents / chemistry
  • Immunosuppressive Agents / metabolism
  • Injections, Intravenous
  • Male
  • Mice
  • Propylene Glycols / administration & dosage*
  • Propylene Glycols / chemistry*
  • Propylene Glycols / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Lysosphingolipid / agonists*
  • Receptors, Lysosphingolipid / metabolism
  • Sphingosine / analogs & derivatives

Substances

  • Immunologic Factors
  • Immunosuppressive Agents
  • Propylene Glycols
  • Receptors, Lysosphingolipid
  • Fingolimod Hydrochloride
  • Sphingosine