Side-by-side · Research reference

AOD-9604vsFOXO4-DRI

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

APhase 2HUMAN-REVIEWED10/47 cited

BAnimal-StrongHUMAN-REVIEWED12/45 cited

AOD-9604

HGH 176-191 · β3-AR Lipolytic

250–300 mcgDaily doseHeffernan 2001

Phase 2Evidence levelHeffernan 2001 Ng 2000

~30 minHalf-life

SQ · Abdomen · Daily fasted

FOXO4-DRI

Senolytic Peptide · D-Retro-Inverso

p53-TADMolecular targetBourgeois 2025

Pre-clinicalDevelopment stage

SQRoute (animal)

SQ · Animal models only

01Mechanism of Action

Parameter

AOD-9604

FOXO4-DRI

Primary target

β3-adrenergic receptor (proposed)Ng 2000

FOXO4-p53 protein complex in senescent cellsBourgeois 2025 Tripathi 2021

Pathway

β3-AR activation → cAMP → hormone-sensitive lipase activation → triglyceride breakdown to FFA + glycerolNg 2000

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

Downstream effect

Lipolysis of adipose tissue triglycerides; FFA release for oxidation; minimal IGF-1 / insulin impactHeffernan 2001

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

Feedback intact?

No GH-axis or IGF-1 feedback

—

Origin

Synthetic modified C-terminal hexadecapeptide fragment of human GH (176-191) with N-terminal Tyr substitutionNg 2000

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

Antibody development

—

02Dosage Protocols

Parameter

AOD-9604

FOXO4-DRI

Standard dose

250–300 mcg / dayHeffernan 2001

Anecdotal SQ range. Phase 2 trial dose 1 mg/day oral.

—

Frequency

Once daily, fasted

—

Lower / starter dose

150 mcg / day

—

Evidence basis

Phase 2 trials + animal-strongHeffernan 2001 Ng 2000

Animal / mechanistic

Duration

8–12 weeks per cycle

Weeks to months (animal studies)

Senescent cell clearance observed within weeks.

Reconstitution

Bacteriostatic water, 1 mL per 2 mg vial → 2 mg/mL

—

Timing

Morning fasted preferred (pre-cardio)

Aligns with circadian lipolysis.

—

Half-life

~30 min plasma

—

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.

Route

—

SQ (animal)

No human route established.

Clinical status

—

No human trials completed

04Side Effects & Safety

Parameter

AOD-9604

FOXO4-DRI

Injection site reaction

Mild erythema

—

GI symptoms

Rare mild nausea

—

Cardiovascular

Possible mild HR increase via β3-AR (theoretical β1 cross-reactivity)

—

IGF-1 elevation

None — designed to lack GH-axis activityHeffernan 2001

—

Insulin sensitivity

Neutral — no glucose impairmentHeffernan 2001

—

Cancer risk

No GH/IGF-1 axis activity → lower theoretical risk vs HGH

—

Pregnancy / OB

Avoid

—

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

Absolute Contraindications

AOD-9604

·Pregnancy / breastfeeding
·Severe cardiovascular disease (caution with β-receptor agonists)

FOXO4-DRI

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

Relative Contraindications

AOD-9604

·Concurrent β-blocker therapy (theoretical antagonism)
·Pheochromocytoma

FOXO4-DRI

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

05Administration Protocol

Parameter

AOD-9604

FOXO4-DRI

1. Reconstitution

Add 1 mL bacteriostatic water to 2 mg vial → 2 mg/mL = 200 mcg per 0.1 mL.

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

2. Injection site

SQ — abdomen preferred. Rotate sites.

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

3. Timing

Morning, fasted, ideally pre-cardio for amplified fat oxidation.

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

4. Storage

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

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

5. Needle

29–31G, 4–8 mm insulin syringe.

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

06Stack Synergy

AOD-9604

+ MOTS-c

Moderate

View MOTS-c →

AOD-9604 mobilises FFAs from adipose via β3-AR; MOTS-c upregulates AMPK / PGC-1α / FAO machinery so that mobilised FFAs are efficiently oxidised. The pathways are sequential — supply (AOD) plus demand (MOTS-c) — and produce more durable lipolytic effects than either alone in anecdotal protocols.

AOD-9604: 250–300 mcg SQ · morning fasted (daily)
MOTS-c: 5 mg SQ · 2–3× per week (pre-workout)
Primary benefit: Fat mobilisation + mitochondrial oxidation, no IGF-1 concern

FOXO4-DRI

— no documented stacks