The clusterin protein is a stress-associated cytoprotective extracellular chaperone that is up-regulated by various apoptotic triggers and confers treatment resistance in various cancers. Among the stress signals that cause up-regulation of clusterin are chemotherapy, irradiation and hormone ablation.
Using the DAC Blockers discovery platform(Kliger et al., 2009), Compugen has identified a novel peptide, CGEN-25008, which corresponds to a segment clusterin. The CGEN-25008 peptide has been shown to bind to the clusterin protein in a dose dependent manner. In vitro, CGEN-25008 evoked growth inhibition of various human cancer cell lines including human non-small cell lung cancer cells as revealed by cellular viability. Furthermore, administration of CGEN-25008 in combination with Taxol has been shown to increase the sensitivity of the cells to Taxol. In a xenograft animal model of lung cancer, CGEN-25008, when given together with Taxol, was shown to reduce tumor size 25% more, in comparison to mice treated with Taxol only.