ES2

Primary Application: Selective Elimination of Senescent (“Zombie”) Cells

Fundamental Information

• Peptide Length: 35 amino acids

• Molecular Weight: 4646.49 Daltons

• Function: High-Potency Senolytic

• Target Mechanism: Disruption of the FOXO4-p53 survival axis

Detailed Overview

ES2 (Enhanced Senescence 2) is a breakthrough “senolytic” peptide designed to solve one of the biggest problems in aging: the accumulation of senescent cells. These are often called “zombie cells” because they stop dividing but refuse to die, instead lingering in the body and secreting inflammatory chemicals that damage healthy neighboring tissue. ES2 works by breaking the “survival bond” between two proteins (FOXO4 and p53) that these zombie cells use to avoid apoptosis.

Once this bond is broken, p53 is released to migrate to the mitochondria and trigger a “clean” programmed cell death (apoptosis). In side-by-side tests, ES2 was found to be 3 to 7 times more powerful than earlier versions of this technology (like FOXO4-DRI). In mouse models, ES2 helped clear damaged cells from the liver, which restored markers of healthy organ function (like Albumin and Cyp3A4) and improved physical fitness. It is also a high-priority research tool for eliminating cancer cells that have survived chemotherapy by entering a senescent state.

Scientific References

1. Le HH, et al. “Molecular modelling of the FOXO4-TP53 interaction to design senolytic peptides for the elimination of senescent cancer cells.” EBioMedicine. 2021;73:103646.

2. Baar MP, et al. “Targeted Apoptosis of Senescent Cells Restores Tissue Homeostasis in Response to Chemotoxicity and Aging.” Cell. 2017;169(1):132-147.