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Project

Validation of small molecule inhibitors of MALT1 protease for the treatment of auto-immune disorders and NF-κB-addicted lymphomas.

Current scientific literature highlights MALT1 protease activity as an important therapeutic target for treating NF-κB-mediated diseases such as autoimmune disorders and lymphoma. In collaboration with CD3 we have developed and patented three classes of MALT1 small molecule inhibitors that affect MALT1 substrate cleavage in cells and that reduce processes regulated by MALT1 protease activity such as IL2 production by and proliferation of activated T cells. We gathered evidence that MALT1 protease activity exerts its function via regulating expression of a distinct subset of NF-κB target genes. First ‘proof of principle’ in vivo was obtained by demonstrating the potential of MALT1inhibitors to stop the progress of experimental autoimmune encephalomyelitis in a mouse model for MS. Clarification of the role of MALT1 protease in restricted NF-κB activation as well as a firm in vivo ‘proof of principle’ of the MALT1 inhibitors in models of autoimmune disease and lymphoma is mandatory in order to establish an industrial valorization via collaboration with Pharmaceutical industry.

Date:1 Oct 2013 →  30 Sep 2014
Keywords:NF-kappaB-addicted lymphomas, auto immune disorders, MALT1 protease
Disciplines:Genetics, Systems biology, Molecular and cell biology