The FOXO4-p53 lead program against “scarred” senescent and cancer cells
Cleara identified that irreparably damaged cells can develop features of scarring. Scarred cells contain nuclear PML/FOXO4-foci, flanked by a modified form of p53, i.e. phosphorylated on S46, T55 and/or S392.
Scarring can occur both in normal cells, and in cancer cells. Cleara pursues projects against scarred cancer and age-related diseases caused by scarred senescent cells.
Scarred cells are enriched in a phosphorylated form of p53. Starting from the natural FOXO4-p53 interaction, Cleara developed two lead candidates, CL04177 and CL04183 that specifically show enhanced binding to this type of phosphorylated p53.
