title: Indolin-2-ones with high in vivo efficacy in a model for multiple sclerosis.
abstract: The known KDR inhibitor SU5416 and several analogues of the indolin-2-one family were surprisingly found to be highly efficacious in the EAE model, an established model for multiple sclerosis. The high in vivo effect could be correlated to in vitro inhibition of the pro-inflammatory cytokine IL-2. Activity following po administration was obtained with several analogues and via the use of prodrugs.
authors.affiliation: LEO Pharma A/S, Industriparken, DK-2750 Ballerup, Denmark. laetitia.bouerat@leo-pharma.com
authors.forename: Laëtitia
authors.initials: L
authors.lastname: Bouérat
authors.forename: Jef
authors.initials: J
authors.lastname: Fensholdt
authors.forename: Xifu
authors.initials: X
authors.lastname: Liang
authors.forename: Sophie
authors.initials: S
authors.lastname: Havez
authors.forename: Simon F
authors.initials: SF
authors.lastname: Nielsen
authors.forename: Jens R
authors.initials: JR
authors.lastname: Hansen
authors.forename: Simon
authors.initials: S
authors.lastname: Bolvig
authors.forename: Christina
authors.initials: C
authors.lastname: Andersson
mesh_terms: D000818:Animals; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000188:drug therapy / Q000378:metabolism*; D066298:In Vitro Techniques; D007211:Indoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D007376:Interleukin-2 / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D009103:Multiple Sclerosis / Q000188:drug therapy / Q000378:metabolism*; D013329:Structure-Activity Relationship; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000037:antagonists & inhibitors
chemical_list: D007211:Indoles; D007376:Interleukin-2; D040301:Vascular Endothelial Growth Factor Receptor-2