The gp96 protein, a member of the family of heat shock proteins, normally resides in the lumen of the endoplasmic reticulum, where its chaperone function plays fundamental roles vital for the proper folding of many proteins. gp96 gains extra-cellular access following cellular stress, and necrotic cell death, The gp96 protein triggers both the innate and adaptive arms of the immune system, and its involvement in inflammatory responses has been demonstrated in recent years, pointing to its potential as a target for therapeutic intervention in the treatment of inflammation and immune-related disorders.
CGEN-25007 is a novel peptide antagonist of gp96 discovered using Compugen’s Disease-Associated Conformation (DAC) Blockers Discovery Platform (Kliger et al., 2009) which is designed for the prediction and selection of peptides that block proteins from adopting their disease-associated conformations. CGEN-25007 exhibited anti-inflammatory activity in both human PBMCs and murine splenocytes challenged with various inflammatory stimuli as well as in an animal model of endotoxemia. CGEN-25007 has also shown positive therapeutic effects in an animal model of inflammatory bowel disease in which it protected mice from the effects of lethal colitis. The above results suggest that CGEN-25007 may thus be a useful therapeutic agent for autoimmune and inflammatory conditions.