What it is
FOXO4-DRI is a large peptide, more than 40 amino acids long. It is made in a lab. Scientists at Erasmus University Medical Center in the Netherlands built it and published it in 2017. It targets senescent cells. These are old or damaged cells that have stopped dividing but do not die. They release signals that cause inflammation. Senescent cells use a protein called FOXO4 to hold on to p53, a protein that tells damaged cells to die. FOXO4-DRI blocks that hold, which frees p53 and lets the senescent cell die. It is built from mirror-image amino acids in reverse order, which enzymes cannot break down. Other names: FOXO4 D-Retro-Inverso, Proxofim.
What researchers study it for
- Removing senescent cells in old mice
- Recovery from chemotherapy damage in mice
- Testosterone production in old mice
- Senescent cells in human cartilage cell cultures
What the studies found
1. Old mice regained fur, kidney function, and activity.
The 2017 study that introduced FOXO4-DRI tested it in naturally old mice. Treated mice had thicker fur, better kidney blood markers, and ran more. It also sped recovery from damage caused by the chemotherapy drug doxorubicin. The mice showed no reported harmful effects at the dose used. Mouse data only.
2. Old mice made more testosterone.
A 2020 study from a separate research group looked at Leydig cells, the cells in the testes that make testosterone. In old mice, many Leydig cells were senescent. FOXO4-DRI cleared those cells, and testosterone rose toward the levels of young mice. Mouse data only.
3. It removed senescent cells from human cartilage cell cultures.
Cartilage cells grown in a lab dish become senescent as they are grown in larger numbers. In this 2021 study, FOXO4-DRI killed the senescent cartilage cells and left the healthy ones alive. This is one of the first tests in human cells. Lab cells only.
4. Experts point to open risks with clearing senescent cells.
This 2020 review from Mayo Clinic researchers compares drugs that clear senescent cells, including FOXO4-DRI. It notes that delivering a large peptide into the body is a challenge. Senescent cells also help stop some early cancer cells, so removing them may carry risks. Results in mice have often not carried over to people for this drug class.
How much research exists
About a dozen animal and lab cell studies. No human trial has been registered or published. No study has measured how the body handles it.
Facts
- Formula: C234H380N76O68S2
- Weight: 5382.1 g/mol
- CAS number: not assigned
- Sequence: mirror-image, reversed segment of the FOXO4 protein
- Time in the blood: never measured
- Storage: freeze the dry powder at -20°C or colder.
Legal status
Not approved by the FDA or any other agency for human use. Banned in sports by WADA under section S0, which covers drugs not approved for human use.
For research use only. Not for human use. Nothing here is medical advice.