Compugen Ltd. ( NASDAQ: CGEN) announced today positive animal model results for CGEN-25068, a novel peptide predicted and selected in silico to block a specific protein-protein interaction known to play an important role in various immune-related disease conditions. CGEN-25068 is one of a number of novel peptides predicted and selected as part of the validation activities for Compugen's Protein-Protein Interaction Blockers (PPI Blockers) Discovery Platform and is the first of these peptides to complete animal model testing. Additional peptides predicted to block targeted interactions in other pathways, primarily cancer-related, are at various stages of validation.
Protein-protein interactions are central to many key biological functions and thus the potential therapeutic applications of inhibiting such interactions are wide-ranging and of high industry interest. However, the discovery of drugs for such targeted therapy is extremely challenging and research efforts to find small molecules that inhibit such protein-protein interactions have been largely unsuccessful.
The PPI Blockers Platform was developed in order to address this need. Through the use of sequence and structure based proprietary algorithms integrated with additional computational biology tools, the Platform identifies potential protein binding segments on the target protein of interest or on proteins predicted to interact with the target protein. The identification and prioritization of these segments then allows the prediction and selection of peptides that could serve as drugs by blocking all, or a portion of, an interacting site. These "blocking peptides" could either serve as therapeutic agents themselves, or be used for the development of therapeutic agents such as monoclonal antibodies.
Using the PPI Blockers Platform, CGEN-25068 was one of several novel peptides predicted to inhibit a specific protein-protein interaction occurring in a protein target expressed on neutrophils and monocytes, and known to play an important role in certain disease conditions by amplifying the immune response. After synthesizing the in silico predicted novel peptides, initial in vitro cell-based validation supported CGEN-25068's effect on the immune response by inhibition of neutrophils' activation. The animal model which was then used for in vivo validation was lipopolysaccharide (LPS)-induced endotoxemia, a model for septic shock, which leads to animal death. In these experiments, CGEN-25068 was shown to significantly increase the survival rate of the animals.Dr. Zurit Levine, Compugen's VP R&D, stated, "We are pleased to report this first animal model validation of a peptide predicted by our PPI Platform to block disease associated protein-protein interactions. The PPI Blockers Platform is now proving to be an important addition to our predictive discovery infrastructure, with recent efforts focused on the identification of novel peptides designed to interfere with protein-protein interactions involved in cancer biology and development. To date, four pathway targets for cancer therapy have entered our Pipeline Program and blocking peptides for each are at various stages of evaluation. These four pathways are related to aspects of cancer growth, metastasis and cancer stem cells, all areas of high industry interest."
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