PRODUCT

FOXO4-DRI (10 mg Vial)

No short description available.

Quickstart Highlights

FOXO4-DRI (also known as Proxofim) is a synthetic D-retro-inverso peptide designed to selectively induce apoptosis in senescent cells by disrupting the FOXO4–p53 protein interaction[1][2]. When this interaction is blocked, p53 translocates to the mitochondria in senescent cells, triggering their programmed death while sparing healthy cells[1]. This educational protocol presents a once-daily subcutaneous approach using a practical dilution for precise insulin-syringe measurements.

Reconstitute: Add 3.0 mL bacteriostatic water → ~3.33 mg/mL concentration.
Typical daily range: 250–500 mcg once daily (gradual titration over 16 weeks).
Easy measuring: At 3.33 mg/mL, 1 unit = 0.01 mL ≈ 33.3 mcg on a U-100 insulin syringe.
Storage: Lyophilized: freeze at −20 °C (−4 °F); after reconstitution, refrigerate at 2–8 °C (35.6–46.4 °F); avoid freeze–thaw cycles[8].

Molecular Info

Chain Length:46 amino acids (D-isoforms)
Sequence Type:D-Retro-Inverso peptide with cell-penetrating domain
Molecular Weight:5,358.2 Da
Amino Acid Sequence:H-ltlrkepaseiaqsileaysqngwanrrsggkrppprrrqrrkkrg-OH (all D-amino acids, lowercase denotes D-form)
Modification:D-Retro-Inverso: Reversed sequence with D-amino acids. Preserves side-chain topology for receptor binding while providing protease resistance. Contains C-terminal HIV-TAT-derived cell-penetrating peptide (RRRQRRKKRG).

Research Indications

Anti Aging

most_effective

Senescent Cell Clearance
Selectively eliminates senescent cells that accumulate with age
Tissue Rejuvenation
Mouse studies show restored tissue function in aged animals

Cellular

effective

Cellular Health
Removes damaged cells to potentially allow regeneration

Inflammation

effective

SASP Reduction
Eliminates cells producing inflammatory senescence factors

Reconstitution

Draw 3.0 mL bacteriostatic water with a sterile syringe.
Inject slowly down the vial wall; avoid foaming.
Gently swirl/roll until dissolved (do not shake) [8] .
Label and refrigerate at 2–8 °C (35.6–46.4 °F) , protected from light.
Gently swirl/roll until dissolved (do not shake)[8].
Label and refrigerate at 2–8 °C (35.6–46.4 °F), protected from light.

Interactions

Rapamycin

Avoid Combination

Rapamycin may interfere with senolytic effects by modulating autophagy and cellular stress responses. A 1-2 week washout period is recommended before FOXO4-DRI administration.

Quercetin

Avoid Combination

Quercetin is itself a senolytic that works through different pathways. Concurrent use may diminish FOXO4-DRI effects. Minimum 96-hour washout, preferably 1-2 weeks.

Dasatinib

Monitor Combination

Dasatinib + Quercetin is an alternative senolytic cocktail. Different mechanism than FOXO4-DRI. Sequential use may be considered but requires washout periods.

Corticosteroids

Avoid Combination

Corticosteroids may suppress the apoptotic cascade required for senolytic activity. Avoid concurrent use; washout period recommended.

Humanin

Compatible

Different mechanisms -Humanin protects healthy cells while FOXO4-DRI clears senescent ones. May be complementary in aging protocols.

MOTS-C

Unknown

Both target aging pathways but through different mechanisms. MOTS-C focuses on metabolic regulation. No interaction studies available.

Epitalon

Unknown

Epitalon works through telomerase activation while FOXO4-DRI eliminates senescent cells. Theoretically complementary but no studies on combination.

5-Amino-1MQ

Unknown

5-Amino-1MQ has some senolytic properties through NNMT inhibition. Different mechanism. No data on concurrent use.

BPC-157

Unknown

BPC-157 promotes tissue repair while FOXO4-DRI eliminates senescent cells. May be complementary for tissue regeneration but no studies available.

Chemotherapy Agents

Synergistic

Mouse studies show FOXO4-DRI protects against doxorubicin-induced liver toxicity and may enhance tumor response when clearing senescent cells post-chemotherapy.

Protocol Overview

Goal:Selectively clear senescent cells via disruption of FOXO4–p53 binding[1][2].
Schedule:Daily subcutaneous injections for 8–16 weeks with gradual dose escalation.
Dose Range:250–500 mcg daily; starting low and titrating upward over time.
Reconstitution:3.0 mL per 10 mg vial (~3.33 mg/mL) for accurate unit measurements.
Storage:Lyophilized frozen at −20 °C (−4 °F); reconstituted refrigerated at 2–8 °C (35.6–46.4 °F); avoid repeated freeze–thaw[8].

Dosage Protocols

Start:250 mcg daily for the first 4 weeks; increase gradually as tolerated.
Mid-Phase:375 mcg daily during Weeks 5–8.
Target:500 mcg daily by Weeks 9–16.
Frequency:Once per day (subcutaneous)[7].
Cycle Length:8–16 weeks; longer cycles may use intermittent dosing schedules as tolerated[4].
Timing:Any consistent time; rotate injection sites to minimize local irritation.

Dosage Protocols

Mouse Research Protocol (IV):5 mg/kgEvery other day × 3 doses
Mouse Research Protocol (IP):5 mg/kgEvery other day × 3 doses
Anecdotal Human Translation (SubQ):~25 mg per injectionEvery other day × 3 doses (75-100 mg total per cycle)

Route:injectable

Storage Instructions

Lyophilized:Store at −20 °C (−4 °F) or below in dry, dark conditions; minimize moisture exposure[8].
Reconstituted:Refrigerate at 2–8 °C (35.6–46.4 °F); use within 1 month when using bacteriostatic water[8].

Important Notes

Practical considerations for consistency and safety.

Use new sterile insulin syringes (typically 29–31 gauge, 0.5 inch needle) for each injection[9]; dispose in a sharps container.
Rotate injection sites (abdomen, thighs, upper arms) at least 1 inch apart to reduce local irritation[10].
Clean the injection site with an alcohol swab and allow to dry before injecting[9].
Inject slowly and steadily; no need to aspirate for subcutaneous injections[11].
Document daily dose and site rotation to maintain consistency throughout the protocol.

Reconstitution

Store lyophilized powder at -20°C until use
Allow vial to reach room temperature before reconstitution
Add sterile water slowly down vial side
Gently swirl until dissolved -do not shake (protein may denature)
Solution should be clear; discard if cloudy or precipitated
Use reconstituted solution within 7-10 days
Store reconstituted at 2-8°C

Route:injectable

How It Works

FOXO4-DRI is a synthetic peptide that selectively targets senescent cells by blocking the FOXO4–p53 protein interaction[1][2]. In normal cells, FOXO4 binds to p53 and sequesters it in the nucleus. In senescent cells, disrupting this interaction causes p53 to translocate to the mitochondria, triggering apoptotic cell death specifically in aged, dysfunctional cells while sparing healthy ones[1]. Animal studies have demonstrated that FOXO4-DRI can reduce senescent cell burden, improve tissue function, and mitigate age-related pathologies[3][4][5]. The peptide’s D-retro-inverso configuration enhances its stability and resistance to proteolytic degradation[2].

Lifestyle Factors

Maintain a balanced, nutrient-dense diet rich in antioxidants and anti-inflammatory compounds.
Combine regular resistance training and cardiovascular activity to support cellular health and metabolic function.
Prioritize sleep quality and stress management, both of which influence cellular senescence pathways.
Stay well-hydrated and avoid excessive alcohol consumption or smoking, which can accelerate cellular aging.

Injection Technique

Clean the vial stopper and skin with alcohol; allow to dry[9].
Pinch a skinfold; insert the needle at 45–90° into subcutaneous tissue (use 90° for adequate fat layer, 45° if thin)[11][12].
Do not aspirate for subcutaneous injections; inject slowly and steadily[11].
Rotate sites systematically (abdomen, thighs, upper arms) to avoid lipohypertrophy and local irritation[10].
Release the pinch and withdraw the needle; apply gentle pressure with gauze if slight bleeding occurs.

Benefits and Side Effects

Benefits

Promotes selective clearance of senescent cells in various tissues, including aged organs and pathological conditions[3][4][5].
Animal studies show improvements in tissue regeneration, reduced inflammation, and enhanced organ function following senescent cell clearance[3][5].
In aged mice, FOXO4-DRI treatment improved testosterone levels and markers of cellular health[3].
No human clinical safety or efficacy data currently exist[6]; tolerability in humans remains uncharacterized.

Side Effects

Injection-site reactions (mild redness, irritation) may occur with subcutaneous administration[10].

FOXO4-DRI (10 mg Vial)

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