Side-by-side · Research reference

CortagenvsFOXO4-DRI

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

AAnimal-MechanisticHUMAN-REVIEWED11/35 cited

BAnimal-StrongHUMAN-REVIEWED12/45 cited

Cortagen

Bioregulatory Tetrapeptide · Khavinson-School

TetrapeptideStructure

↓ LPO productsAntioxidant effectKozina 2007

AnimalEvidence level

Injectable · Animal models

FOXO4-DRI

Senolytic Peptide · D-Retro-Inverso

p53-TADMolecular targetBourgeois 2025

Pre-clinicalDevelopment stage

SQRoute (animal)

SQ · Animal models only

01Mechanism of Action

Parameter

Cortagen

FOXO4-DRI

Primary target

Cerebral cortex tissue — molecular targets under investigation

FOXO4-p53 protein complex in senescent cellsBourgeois 2025 Tripathi 2021

Pathway

Antioxidant pathway modulation — suppression of LPO cascade, reduction of protein oxidative modificationKozina 2007

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

Downstream effect

Decreased lipid peroxidation products, reduced oxidative protein damage, altered gene expression in cardiac tissueKozina 2007 Anisimov 2004

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

Feedback intact?

—

Origin

Synthetic tetrapeptide derived from amino acid analysis of natural brain cortex peptide preparation CortexinAnisimov 2004

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

Antibody development

—

02Dosage Protocols

Parameter

Cortagen

FOXO4-DRI

Animal model dose (rat)

Injection protocol (dose not specified in abstracts)

Multiple injections over study period.

—

Avian model dose (chicken)

40-day injection courseKuznik 2008

Compared to epithalon in hypophysectomized and aged birds.

—

Human peripheral nerve study

Therapeutic course (protocol details not provided)

Posttraumatic recovery context — reference cited but not detailed.

—

Evidence basis

Animal mechanistic studies

Animal / mechanistic

Route

Injectable (inferred from animal protocols)

SQ (animal)

No human route established.

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.

Duration

—

Weeks to months (animal studies)

Senescent cell clearance observed within weeks.

Clinical status

—

No human trials completed

04Side Effects & Safety

Parameter

Cortagen

FOXO4-DRI

Antioxidant suppression

Suppression of antioxidant activity noted alongside LPO reductionKozina 2007

Mechanism unclear — possible homeostatic adaptation.

—

Immune/hemostasis effects

No effect on immunity or hemostasis parameters in avian hypophysectomy model (unlike epithalon)Kuznik 2008

Epithalon reversed deficits; cortagen did not.

—

Human safety data

No adverse events reported in peripheral nerve recovery context

Limited detail in available abstracts.

—

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

Cortagen

—

FOXO4-DRI

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

Relative Contraindications

Cortagen

—

FOXO4-DRI

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

05Administration Protocol

Parameter

Cortagen

FOXO4-DRI

1. Preparation

Reconstitute lyophilised peptide with bacteriostatic water per supplier protocol. Exact volumes depend on concentration supplied.

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

2. Injection site

Subcutaneous injection typical for bioregulatory peptides — abdomen or thigh. Rotate sites.

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

3. Timing

Animal protocols used repeated dosing over weeks. Human timing not established — evening administration common in Khavinson tradition.

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

4. Storage

Lyophilised: refrigerate or freeze per supplier. Reconstituted: refrigerate 2–8 °C, use within guideline window.

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.