Side-by-side · Research reference
DihexavsFOXO4-DRI
Side-by-side comparison across mechanism, dosage, evidence, side effects, administration, and stack synergies. Citations on every claim where available.
AAnimal-StrongHUMAN-REVIEWED7/28 cited
BAnimal-StrongHUMAN-REVIEWED12/45 cited
Dihexa
Angiotensin IV Analogue · Pre-Clinical
Not established — animal studies only
FOXO4-DRI
Senolytic Peptide · D-Retro-Inverso
SQ · Animal models only
01Mechanism of Action
Parameter
Dihexa
FOXO4-DRI
Primary target
c-Met receptor (HGF receptor tyrosine kinase)
FOXO4-p53 protein complex in senescent cellsBourgeois 2025Tripathi 2021
Pathway
HGF/c-Met receptor activation → downstream signaling cascade → synaptogenesis and dendritic arborization
FOXO4-DRI binds disordered p53 transactivation domain → displaces FOXO4 → nuclear p53 exclusion → p53-mediated apoptosis in senescent cells
Downstream effect
Induction of dendritic arborization, synapse formation, neurogenesis, and neuroprotection in rodent models
Selective apoptosis of senescent cells; clearance restores tissue homeostasisTripathi 2021Alameen 2026
Feedback intact?
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—
Origin
Small-molecule angiotensin IV analogue designed to activate HGF/c-Met systemWright 2015
D-retro-inverso modification — inverted amino acid sequence, D-amino acids for protease resistance
Antibody development
—
—
02Dosage Protocols
Parameter
Dihexa
FOXO4-DRI
Human dosing
Not established — no human trials
—
Animal studies
Mouse/rat models only — dosing not translatable to humans
—
Evidence basis
Pre-clinical / Rodent models
Animal / mechanistic
Clinical status
No Phase 1, 2, or 3 trials published
No human trials completed
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.
Duration
—
Weeks to months (animal studies)
Senescent cell clearance observed within weeks.
04Side Effects & Safety
Parameter
Dihexa
FOXO4-DRI
Human safety data
None available — no human clinical trials
—
Theoretical c-Met risks
c-Met receptor activation has been implicated in tumorigenesis; unknown cancer risk profile
—
Pre-clinical tolerability
Not systematically reported in available studies
—
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
Dihexa
- ·Not approved for human use — research compound only
FOXO4-DRI
- ·Pulmonary hypertension or vascular disease (preclinical evidence of harm)Born 2023
- ·Pregnancy / lactation (no safety data)
Relative Contraindications
Dihexa
- ·Theoretical contraindication: active or history of malignancy (c-Met pathway involvement in cancer)
FOXO4-DRI
- ·Active malignancy (senescence as tumour suppressor mechanism)
- ·Wound healing / tissue repair (senescent cells involved in fibrosis resolution)
05Administration Protocol
Parameter
Dihexa
FOXO4-DRI
1. Human administration
No established protocol. Dihexa has not been tested in human subjects. Animal studies used various routes (typically subcutaneous or intraperitoneal in rodents) not translatable to clinical use.
Subcutaneous injection used in rodent models. No human administration protocol exists.
2. Legal status
Pre-clinical research compound. Not approved by FDA or any regulatory authority for human use.
Typically reconstituted in sterile saline or PBS for animal experiments. Stability data limited.
3. Dosing schedule
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Variable — single bolus or intermittent dosing over weeks. No standardised human protocol.
4. Clinical development status
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No registered human trials. Commercialisation by Cleara Biotech (Netherlands) in development phase.
5. Safety monitoring (proposed)
—
Would require cardiovascular assessment, pulmonary function, immune panel, tumour surveillance if human trials proceed.