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Selective CD40-TRAF6 inhibitors for the treatment of inflammatory diseases

27.05.2014

The co-stimulatory CD40-CD40L dyad is crucial in the development and progression of immune responses and chronic inflammatory diseases, such as atherosclerosis, obesity and multiple sclerosis. However, long-term antibody-mediated inhibition of CD40L or CD40 is not clinically feasible as it results in thromboembolic events and severe immune suppression. More downstream inhibition of the CD40L-CD40 pathway is therefore preferable, especially tumor necrosis factor receptor-associated factors (TRAFs) recruited by CD40. Here we created a set of inhibitors that selectively block CD40-TRAF6 interactions. The rest of the CD40 cascade is left unaffected preventing unwanted immune-suppressive side effects. Therefore, our new inhibitors offer promising candidates as therapeutic agents for the treatment of chronic inflammatory diseases, such as atherosclerosis, obesity and multiple sclerosis.

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