Therapeutic dosing of an orally active, selective @entity25491 inhibitor suppresses disease in models of XXXX .

@entity630 @entity309 @entity66 @entity19 @entity61 @entity1753 @entity15 @entity6503 @entity468 @entity25491 @entity792 @entity9749 @entity72678
The purpose of the study was to examine the potential of inhibition of @entity25491 as a treatment for @entity792 . A highly selective @entity25491 inhibitor, @entity72678 , was shown to upregulate levels of the @entity25491 substrate, invariant chain Lip10, in vitro as well as in vivo in C57Bl/6 @entity19 after oral administration. Functional activity of the compound was shown by a reduction in the OVA-specific response of OVA-sensitized splenocytes from C57Bl/6 @entity19 as well as from OVA-TCR @entity19 (DO11.10). Since these studies revealed a selective suppression of the @entity630 and Th17 cytokines causing a shift to @entity61 , @entity72678 was tested in the @entity19 HC-gp39-immunization model. Indeed, @entity72678 specifically reduced the circulating HC-gp39-specific @entity9749 in these @entity19 indicating selective inhibition of the @entity630 type of response in vivo. The importance of especially the @entity630 and Th17 cell subsets in the pathology of @entity792 , renders @entity468 inhibition a highly interesting potential therapeutic treatment of @entity792 . Therefore, @entity72678 was tested in a @entity19 model of @entity15 (i.e. @entity6503 ( @entity6503 )) in a semi-therapeutic setting (ie. oral treatment after initial sensitization to antigen). Finally, in a @entity19 model with features resembling @entity309 (the @entity1753 ( @entity1753 ) model), @entity72678 was tested in a therapeutic manner (after disease development). @entity72678 caused a significant @entity66 score in both disease models, indicating a promising role for @entity468 inhibitors in the area of therapeutic treatments for @entity792 .
