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Autoimmune disease; cachexia

Tumor necrosis factor-a (TNF-a)

Biochemical and cell culture studies identified a bicyclic peptide inhibitor of TNF-a that could help treat cachexia and autoimmune disease. TNF-a is upregulated in cachexia and multiple autoimmune diseases. A screen of a library of bicyclic peptides yielded a candidate that selectively bound TNF-a with a Kd value of 0.45 mM.
In an ELISA, the peptide inhibited the interaction between TNF-a and TNF receptor 1 (TNFRSF1A; TNFR1; CD120a). In cultured fibroblasts, the bicyclic peptide decreased TNF-a-induced cell death compared with monocyclic and linear peptides. Next steps include optimizing the potency and pharmacological properties of the inhibitor.

SciBX 6(33); doi:10.1038/scibx.2013.902
Published online Aug. 29, 2013

Patent application filed; available for licensing

Lian, W. et al. J. Am. Chem. Soc.; published online July 18, 2013;
Contact: Dehua Pei, The Ohio State University, Columbus, Ohio