Indolin-2-ones with high in vivo efficacy in a model for multiple sclerosis.
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.
Bouérat
Laëtitia
L
LEO Pharma A/S, Industriparken, DK-2750 Ballerup, Denmark. laetitia.bouerat@leo-pharma.com
Fensholdt
Jef
J
Liang
Xifu
X
Havez
Sophie
S
Nielsen
Simon F
SF
Hansen
Jens R
JR
Bolvig
Simon
S
Andersson
Christina
C
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
D007211:Indoles; D007376:Interleukin-2; D040301:Vascular Endothelial Growth Factor Receptor-2