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Salicylanilides: selective inhibitors of interleukin-12p40 production
Michael E Brown1, Jeffrey N Fitzner, Tracey Stevens
1Medicinal Chemistry, Amgen Inc., 1201 Amgen Court West, Seattle, WA 98119, USA.
Abstract:
Interleukin (IL)-12p40, a subunit component of both IL-12 and IL-23, is being widely studied for its role in inflammatory disease. As part of an effort to profile cellular signaling pathways across different cell types, we report salicylanilide inhibitors of IL-12p40 production in stimulated dendritic cells. Based on a hypothesis that a desirable therapeutic profile is one that could block IL-12p40 but not IL-6 production, we engaged in directed analoging. This resulted in salicylanilides with similar IL-12p40 related potency but enhanced selectivity relative to IL-6 production.
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