CPP-CAND

Primary Application: Preventing Cancer Recurrence and Therapy-Induced Aging

Fundamental Information

• Composition: p53-mimetic domain (CAND) + HIV-TAT Cell Penetrating sequence

• Function: Selective destruction of senescent/quiescent, non-proliferating chemo-resistant cells

• Key Advantage: Enhanced entry into cell nuclei via TAT-fusion

• Design Method: NMR spectroscopy and Alanine screening

Detailed Overview

CPP-CAND is a “next-generation” senolytic peptide that reverses the traditional approach to clearing aging cells. While most peptides in this class try to mimic the FOXO4 protein, CPP-CAND mimics the p53 protein instead. This “p53-mimetic” approach allows the peptide to bind to its target with very high accuracy. To ensure the peptide actually gets inside the cell nucleus where it is needed, it is fused to a “carrier” sequence (HIV-TAT) that acts as a molecular key to penetrate the cell membrane.

This peptide is particularly effective at clearing out cancer cells that have survived chemotherapy (such as cisplatin or doxorubicin) by entering a state called “therapy-induced senescence.” These dormant cells are dangerous because they can eventually wake back up and cause the cancer to return. CPP-CAND selectively hunts these cells down and forces them to self-destruct while leaving healthy, normal cells completely untouched. Because of its efficient design and shorter length, it is viewed as a highly cost-effective and precise candidate for researching ways to eliminate residual disease after standard treatments.

Scientific References

1. Kang D, et al. “Peptide Inhibitors Targeting FOXO4-p53 Interactions and Inducing Senescent Cancer Cell-specific Apoptosis.” Journal of Medicinal Chemistry. 2025;68(15):15683-15694.

2. Kang D, et al. “Mechanistic Insights into DNA Recognition by FOXO4 and Development of a Peptide Targeting Senescent Cells via FOXO4-p53 Inhibition.” GIST Scholar. 2025.