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.
MeSH terms
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Animals
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Encephalomyelitis, Autoimmune, Experimental / drug therapy
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Encephalomyelitis, Autoimmune, Experimental / metabolism*
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In Vitro Techniques
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Indoles / chemical synthesis*
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Indoles / chemistry
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Indoles / pharmacology
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Interleukin-2 / antagonists & inhibitors
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Interleukin-2 / biosynthesis
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Leukocytes, Mononuclear / drug effects
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Leukocytes, Mononuclear / metabolism
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Mice
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Multiple Sclerosis / drug therapy
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Multiple Sclerosis / metabolism*
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Structure-Activity Relationship
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Vascular Endothelial Growth Factor Receptor-2 / antagonists & inhibitors
Substances
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Indoles
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Interleukin-2
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Vascular Endothelial Growth Factor Receptor-2