- subcutaneous
FOXO4-DRI
FOXO4 D-Retro-Inverso Peptide (Proxofim)
FOXO4-DRI at a glance
Not on either FDA listHow studies gave it
Injected into the fat under the skin
Evidence on this page
3 peer-reviewed papers, published 2017 to 2021
FDA compounding lists
It appears on neither of the two FDA compounding tables.
What it is
A synthetic 46-amino-acid D-retro-inverso cell-penetrating peptide designed to disrupt the FOXO4-p53 interaction in senescent cells. FOXO4-DRI competitively binds p53's disordered transactivation domain 2, releasing p53 from FOXO4 sequestration in PML nuclear bodies and triggering caspase-3/7-dependent intrinsic apoptosis selectively in senescent cells.
The DRI modification (reversed sequence, all D-amino acids) confers protease resistance while preserving binding topology. The C-terminal HIV-TAT-derived sequence enables cellular uptake. Studied in mouse models of accelerated aging, chemotoxicity, and natural aging (Baar et al., Cell 2017), where it was observed to restore fur density, renal function, and exploratory behavior. No human clinical trials have been conducted.
Published research
The landmark Baar et al. 2017 Cell study demonstrated that FOXO4-DRI (5 mg/kg IP, 3 doses on alternating days) selectively cleared senescent cells and restored tissue homeostasis in fast-aging XpdTTD/TTD mice, doxorubicin-treated mice, and naturally aged mice. A 2020 follow-up (Zhang et al., Aging) showed the peptide alleviated age-related testosterone insufficiency by targeting senescent Leydig cells.
A 2025 structural study (Bourgeois et al., Nature Communications) characterized the binding mechanism between FOXO4-DRI and the disordered p53 transactivation domain. In vitro studies show 11.7-fold selectivity for senescent over non-senescent fibroblasts. No peer-reviewed human clinical trials have been conducted as of March 2026.
Community dosing protocols are allometrically scaled from mouse data and are not clinically validated.
What the terms on this page mean5 termsHide
- peptide
- A short chain of amino acids, the building blocks of proteins.
- amino acid
- A building block that links with others to form peptides and proteins.
- clinical trial
- A study that tests something in people under a written plan, with results recorded.
- in vitro
- In a dish. Cells or tissue tested outside a living body.
- fibroblast
- The cell in skin and connective tissue that makes collagen and repairs damage.
Compounding status
Not on either FDA list- FDA listing
- FOXO4-DRI appears on neither FDA's category 2 table nor its table of withdrawn nominations.
- What that means
- Absence from both lists is not permission to compound. Section 503A allows a bulk drug substance only where a USP or NF monograph exists, or the substance is a component of an FDA-approved drug product, or it appears on the 503A bulks list.
Source: Certain Bulk Drug Substances for Use in Compounding that May Present Significant Safety Risks, FDA. Content current as of 2026-04-22; read 2026-09-05. This describes what a compounding pharmacy may supply. It is not advice about your own use.
Also given subcutaneous
- GHK-CuCopper Peptide GHK-CuNomination withdrawn
- GHRP-2Growth Hormone Releasing Peptide-2 (Pralmorelin)FDA category 2
- GHRP-6Growth Hormone Releasing Peptide-6FDA category 2
- HexarelinExamorelin (Hexarelin, EP-23905)Not on either FDA list
- HumaninHumanin (HN) — Mitochondrial-Derived PeptideNot on either FDA list
- IGF-1 DESdes(1-3) Insulin-like Growth Factor-1Not on either FDA list
Where this came from3 referencesHide
Each one was resolved at PubMed and confirmed to be the work this page cites. Author, title, journal and year come from the PubMed record, not from the page text.
- Targeted Apoptosis of Senescent Cells Restores Tissue Homeostasis in Response to Chemotoxicity and Aging
Baar MP, et al.. Cell (2017). PMID 28340339.
- FOXO4-DRI alleviates age-related testosterone secretion insufficiency by targeting senescent Leydig cells in aged mice
Zhang C, et al.. Aging (2020). PMID 31959736.
- Senolytic Peptide FOXO4-DRI Selectively Removes Senescent Cells From in vitro Expanded Human Chondrocytes
Huang Y, et al.. Frontiers in bioengineering and biotechnology (2021). PMID 33996787.
About this page
Reviewed 2026-08-11. This page reports what published studies and FDA documents say. It carries no dose, cycle length or stack, and it does not tell you whether a substance is appropriate for you. Side-effect reports circulating on forums are self-reported rather than measured, so they are not republished here.
See the editorial policy for how corrections are handled.