Klotho (KP1) vs FOXO4-DRI
Klotho (KP1) and FOXO4-DRI both appear in cellular senescence research, from opposite directions. FOXO4-DRI is a modified peptide designed to make senescent cells die, by breaking the bond between the proteins FOXO4 and p53. KP1, a 30-amino-acid piece of the Klotho protein, lowered senescence markers in diseased mouse kidneys by restoring the kidneys' own Klotho. This page compares them as research compounds.
Not yet stocked
Register interest
Klotho (KP1) is not currently supplied by Peptx. Leave an email address and we will notify you once verified reference material is available. No purchase, no obligation, and the address is used for this notice only.
| Klotho (KP1) | FOXO4-DRI | |
|---|---|---|
| What it is | 30-amino-acid fragment of human alpha-Klotho | Modified FOXO4 peptide (D-retro-inverso) |
| Main target | TGF-beta receptor 2 | The FOXO4 and p53 interaction |
| Effect on senescent cells | Fewer senescence markers (p21, p16, γ-H2AX) in fibrotic mouse kidneys | Triggers apoptosis of senescent cells (a senolytic) |
| Key study | Theranostics, 2024 | Cell, 2017 |
| Human data | None | None registered |
| Peptx availability | Not stocked, waitlist on this page | Factory Direct kits |
- What it is
- 30-amino-acid fragment of human alpha-KlothoModified FOXO4 peptide (D-retro-inverso)
- Main target
- TGF-beta receptor 2The FOXO4 and p53 interaction
- Effect on senescent cells
- Fewer senescence markers (p21, p16, γ-H2AX) in fibrotic mouse kidneysTriggers apoptosis of senescent cells (a senolytic)
- Key study
- Theranostics, 2024Cell, 2017
- Human data
- NoneNone registered
- Peptx availability
- Not stocked, waitlist on this pageFactory Direct kits
Remove the cells, or change their state
Senescent cells have stopped dividing but stay in tissue and release inflammatory signals. FOXO4-DRI was designed in 2017 to remove them. In senescent cells FOXO4 holds p53 in the nucleus and keeps the cell alive; the peptide breaks that bond, p53 moves out of the nucleus and the cell undergoes apoptosis. In mice it countered chemotherapy damage and restored some measures of tissue health in fast-ageing and naturally aged animals.
KP1 was not designed to remove senescent cells. In a 2024 study of mouse chronic kidney disease, it lowered the senescence markers p21, p16 and γ-H2AX in kidney tubule cells. The authors linked this to restored Klotho production, through a microRNA (miR-223-3p) that blocks Klotho and that KP1 counteracted.
How strong is the evidence?
Both rest on animal studies. FOXO4-DRI has one landmark mouse paper and no registered human trials. KP1 has five cell and mouse studies, all from the group that discovered it, and no human trials. No study has compared them.
Bottom line for research labs
FOXO4-DRI and Klotho (KP1) approach senescence from opposite ends. FOXO4-DRI removes senescent cells and is the better-known senolytic peptide. KP1 is a TGF-beta receptor blocker whose effect on senescence markers was seen in one mouse kidney study. Both are animal-stage research compounds.