The "Blockers of Disease-Associated Conformation" (DAC Blockers) platform is a discovery platform for the design of peptides that block proteins from adopting their disease-associated conformations.
The DAC Blockers platform has been designed to identify segments in proteins of interest that, if introduced therapeutically as synthetic peptides, would block specific conformational changes of such proteins, and thereby prevent them from adopting disease-associated conformations and related activities (Kliger et al., 2009). A key capability of the platform is that it enables the proteome-wide search for such conformational change blocking peptides in human, viral and bacterial proteomes. Initial runs of the discovery platform resulted in the in silico prediction of therapeutic peptide candidates for approximately 40 drug targets of interest with potential usage for various indications, including solid cancers, inflammatory diseases, septic shock and viral diseases. Eleven of these drug targets were selected for initial experimental validation and potential peptide blockers were found for all eleven targets.
In addition, to date, three of these peptides have shown biological efficacy in additional experimental models, further demonstrating both their potential therapeutic utility and the validity of the platform's predictive capability. These include CGEN-25007, CGEN-25008, and CGEN-25017.