Side-by-side · Research reference

FOXO4-DRIvsGHRP-2

Side-by-side comparison across mechanism, dosage, evidence, side effects, administration, and stack synergies. Citations on every claim where available.

AAnimal-StrongHUMAN-REVIEWED12/45 cited

BPhase 2HUMAN-REVIEWED15/42 cited

FOXO4-DRI

Senolytic Peptide · D-Retro-Inverso

p53-TADMolecular targetBourgeois 2025

Pre-clinicalDevelopment stage

SQRoute (animal)

SQ · Animal models only

GHRP-2

Hexapeptide GHRP · Phase 2 (clinical diagnostic)

100–300 mcgPer doseBowers 1990

Phase 2Evidence levelBowers 1990 Sigalos 2018

~30 minHalf-lifeMalagón 1999

SQ · Multiple sites · 1–3×/day

01Mechanism of Action

Parameter

FOXO4-DRI

GHRP-2

Primary target

FOXO4-p53 protein complex in senescent cellsBourgeois 2025 Tripathi 2021

Ghrelin receptor (GHS-R1a) on anterior pituitaryBowers 1990

Pathway

FOXO4-DRI binds disordered p53 transactivation domain → displaces FOXO4 → nuclear p53 exclusion → p53-mediated apoptosis in senescent cells

GHS-R1a → Gαq → Ca²⁺ → GH vesicle exocytosisBowers 2002

Downstream effect

Selective apoptosis of senescent cells; clearance restores tissue homeostasisTripathi 2021 Alameen 2026

Strong GH pulse + IGF-1 elevation; appetite increase via ghrelin agonismBowers 2002

Feedback intact?

—

Yes, with somatostatin feedback active

Origin

D-retro-inverso modification — inverted amino acid sequence, D-amino acids for protease resistance

Synthetic hexapeptide; developed by Bowers/Tulane group in the 1980sBowers 1990

Antibody development

—

02Dosage Protocols

Parameter

FOXO4-DRI

GHRP-2

Animal dose (mouse)

5 mg/kg

SQ injection, aged mouse model (testosterone restoration).

—

Frequency (animal)

Variable — single or intermittent dosing

Protocol-dependent; no standardised regimen.

—

Human equivalent (theoretical)

~0.4 mg/kg (28 mg / 70 kg adult)

Extrapolated using allometric scaling; no clinical validation.

—

Evidence basis

Animal / mechanistic

Phase 2 + clinical diagnostic useBowers 1990

Route

SQ (animal)

No human route established.

—

Duration

Weeks to months (animal studies)

Senescent cell clearance observed within weeks.

8–12 weeks on / 4 off (anecdotal)

Clinical status

No human trials completed

—

Standard dose

—

100–300 mcg per injectionBowers 1990

Frequency

—

1–3× per day

Lower / starter dose

—

50 mcg per dose

Reconstitution

—

Bacteriostatic water

Timing

—

Pre-sleep + fasted preferred

Half-life

—

~30 minMalagón 1999

04Side Effects & Safety

Parameter

FOXO4-DRI

GHRP-2

Pulmonary hypertension risk

Senescent cell elimination promoted PH development/progression in rodent modelsBorn 2023

—

Context-dependent toxicity

Beneficial effects may be tissue/context-specific; elimination not universally protectiveBorn 2023

—

Off-target apoptosis

Theoretical risk of non-senescent cell apoptosis (selectivity not absolute)

—

Immune perturbation

Senescent cells contribute to immune surveillance; clearance effects unknown

—

Human safety unknown

No clinical trials — toxicity profile in humans not established

—

Cortisol elevation

—

Mild but measurableBowers 1990

Prolactin elevation

—

Mild but measurable

Hunger

—

Strong appetite increase

Injection site reaction

—

Mild erythema

IGF-1 elevation

—

Strong; monitor with chronic high-dose use

Cancer risk

—

Contraindicated in active malignancy

Pregnancy / OB

—

Avoid

Absolute Contraindications

FOXO4-DRI

·Pulmonary hypertension or vascular disease (preclinical evidence of harm)Born 2023
·Pregnancy / lactation (no safety data)

GHRP-2

·Active malignancy
·Pregnancy / breastfeeding

Relative Contraindications

FOXO4-DRI

·Active malignancy (senescence as tumour suppressor mechanism)
·Wound healing / tissue repair (senescent cells involved in fibrosis resolution)

GHRP-2

·Untreated diabetes

05Administration Protocol

Parameter

FOXO4-DRI

GHRP-2

1. Pre-clinical route

Subcutaneous injection used in rodent models. No human administration protocol exists.

Add 2 mL bacteriostatic water to 5 mg vial → 2.5 mg/mL.

2. Reconstitution (animal)

Typically reconstituted in sterile saline or PBS for animal experiments. Stability data limited.

SQ — abdomen or thigh. Rotate sites.

3. Dosing schedule

Variable — single bolus or intermittent dosing over weeks. No standardised human protocol.

Pre-sleep + fasted preferred.

4. Clinical development status

No registered human trials. Commercialisation by Cleara Biotech (Netherlands) in development phase.

Lyophilised: room temp, light-protected. Reconstituted: refrigerate ≤30 days.

5. Safety monitoring (proposed)

Would require cardiovascular assessment, pulmonary function, immune panel, tumour surveillance if human trials proceed.

29–31G, 4–8 mm insulin syringe.

06Stack Synergy

FOXO4-DRI

— no documented stacks

GHRP-2

+ CJC-1295 (no DAC)

Strong

View CJC-1295 (no DAC) →

GHRP-2 + CJC-1295-no-DAC is a higher-amplitude alternative to the ipamorelin + CJC-1295 stack. GHRP-2 produces a stronger pulse but with cortisol + prolactin signal — choose when maximum GH amplitude is the goal and the side-effect tolerance is acceptable.

GHRP-2: 100–200 mcg SQ · pre-sleep
CJC-1295 (no DAC): 100 mcg SQ · same injection
Primary benefit: High-amplitude GH pulse, body composition

Bowers 1990 Teichman 2006