title: Potent S1P receptor agonists replicate the pharmacologic actions of the novel immune modulator FTY720.
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.
authors.affiliation: Department of Medicinal Chemistry, Merck Research Laboratories, Rahway, NJ 07065, USA. jeffrey_hale@merck.com
authors.forename: Jeffrey J
authors.initials: JJ
authors.lastname: Hale
authors.forename: William
authors.initials: W
authors.lastname: Neway
authors.forename: Sander G
authors.initials: SG
authors.lastname: Mills
authors.forename: Richard
authors.initials: R
authors.lastname: Hajdu
authors.forename: Carol
authors.initials: C
authors.lastname: Ann Keohane
authors.forename: Mark
authors.initials: M
authors.lastname: Rosenbach
authors.forename: James
authors.initials: J
authors.lastname: Milligan
authors.forename: Gan-Ju
authors.initials: GJ
authors.lastname: Shei
authors.forename: Gary
authors.initials: G
authors.lastname: Chrebet
authors.forename: James
authors.initials: J
authors.lastname: Bergstrom
authors.forename: Deborah
authors.initials: D
authors.lastname: Card
authors.forename: Gloria C
authors.initials: GC
authors.lastname: Koo
authors.forename: Sam L
authors.initials: SL
authors.lastname: Koprak
authors.forename: Jesse J
authors.initials: JJ
authors.lastname: Jackson
authors.forename: Hugh
authors.initials: H
authors.lastname: Rosen
authors.forename: Suzanne
authors.initials: S
authors.lastname: Mandala
mesh_terms: D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D000068876:Fingolimod Hydrochloride; D006801:Humans; D007155:Immunologic Factors / Q000008:administration & dosage* / Q000737:chemistry* / Q000378:metabolism; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism; D007275:Injections, Intravenous; D008297:Male; D051379:Mice; D011409:Propylene Glycols / Q000008:administration & dosage* / Q000737:chemistry* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D049349:Receptors, Lysosphingolipid / Q000819:agonists* / Q000378:metabolism; D013110:Sphingosine / Q000031:analogs & derivatives
chemical_list: D007155:Immunologic Factors; D007166:Immunosuppressive Agents; D011409:Propylene Glycols; D049349:Receptors, Lysosphingolipid; D000068876:Fingolimod Hydrochloride; D013110:Sphingosine