FOXO4-DRI
FOXO4-DRI (a D-retro-inverso peptide, sometimes called proxofim) came to prominence with a 2017 study showing it could selectively clear senescent cells and improve markers of health and fitness in aged and progeroid mice. It is a preclinical research tool in the senolytics field; it has not been evaluated in completed human clinical trials and is not an approved therapeutic.
Mechanism
In plain terms, FOXO4-DRI is built to push worn-out 'senescent' cells into self-destruction while sparing healthy cells. Technically, it is a synthetic peptide based on the FOXO4 sequence, made from D-amino acids in reversed order (a D-retro-inverso design) to resist degradation. It interferes with the binding of FOXO4 to the tumour-suppressor protein p53; in senescent cells this is reported to release p53 to the mitochondria and trigger apoptosis (programmed cell death), selectively removing senescent cells. These effects have been demonstrated in cell and animal models only.
Regulatory Status by Region
- United States (FDA)Not FDA-approved; an experimental senolytic peptide with no approved therapeutic use, and preclinical only.
- Australia (TGA)Not on the ARTG; an unapproved experimental substance.
- European Union (EMA)No EMA marketing authorisation; not an approved medicine in the EU.
- WADANot named on the Prohibited List, but as a non-approved substance it falls under S0 (Non-Approved Substances), prohibited at all times; athletes should treat it as prohibited.
Key Studies
- Targeted Apoptosis of Senescent Cells Restores Tissue Homeostasis in Response to Chemotoxicity and Aging (Baar MP, Brandt RMC, Putavet DA, et al. Cell. 2017;169(1):132-147.e16. PMID 28340339)