Side-by-side · Research reference

FOXO4-DRIvsTB-500

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-REVIEWED8/46 cited

FOXO4-DRI

Senolytic Peptide · D-Retro-Inverso

p53-TADMolecular targetBourgeois 2025

Pre-clinicalDevelopment stage

SQRoute (animal)

SQ · Animal models only

TB-500

Thymosin β4 fragment · Healing

2 mgPer doseGoldstein 2012

Phase 2Evidence levelGoldstein 2012

~2 hrHalf-life

SQ or IM · Multiple sites · 2–3×/week

01Mechanism of Action

Parameter

FOXO4-DRI

TB-500

Primary target

FOXO4-p53 protein complex in senescent cellsBourgeois 2025 Tripathi 2021

G-actin (sequestering) + cell-surface integrinsGoldstein 2012

Pathway

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

Actin remodelling → cell migration; integrin-linked signaling → angiogenesis; anti-inflammatory cytokine modulationGoldstein 2012 Malinda 1999

Downstream effect

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

Accelerated wound healing, endothelial migration, hair follicle regeneration, cardiac repair (preclinical)Goldstein 2012

Feedback intact?

—

Endogenous protein at baseline; supplementation amplifies

Origin

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

17-AA active fragment of endogenous 43-AA thymosin β4 (TMSB4X gene)Goldstein 2012

Antibody development

—

02Dosage Protocols

Parameter

FOXO4-DRI

TB-500

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

Animal-strong + Phase 2 dermal/ocular trialsGoldstein 2012

Route

SQ (animal)

No human route established.

—

Duration

Weeks to months (animal studies)

Senescent cell clearance observed within weeks.

4–8 weeks loading; longer maintenance for chronic injury

Clinical status

No human trials completed

—

Standard dose

—

2 mg per injectionGoldstein 2012

Anecdotal community range; clinical Phase 2 trials used 70–840 mcg/kg IV.

Frequency

—

2× per week (loading); then 1× per week (maintenance)

Lower / starter dose

—

1 mg per injection

Reconstitution

—

Bacteriostatic water, 1–2 mL per 5 mg vial

Timing

—

Evening or pre-rest preferred (anecdotal)

Half-life

—

~2 hours (estimated; tissue uptake longer)

04Side Effects & Safety

Parameter

FOXO4-DRI

TB-500

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

—

Injection site reaction

—

Mild erythema, transient pain

GI symptoms

—

Rare nausea (anecdotal)

Cancer risk

—

Theoretical via angiogenesis pathway

Lethargy / fatigue

—

Reported anecdotally during loading phase

Antibody formation

—

No data (no long-term human trials)

Pregnancy / OB

—

Avoid

Long-term safety

—

Unknown beyond Phase 2

Absolute Contraindications

FOXO4-DRI

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

TB-500

·Active malignancy (theoretical angiogenesis concern)
·Pregnancy / breastfeeding

Relative Contraindications

FOXO4-DRI

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

TB-500

·Cancer history
·Concurrent VEGF inhibitor therapy

05Administration Protocol

Parameter

FOXO4-DRI

TB-500

1. Pre-clinical route

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

Add 1–2 mL bacteriostatic water to 5 mg vial → 2.5–5 mg/mL. Roll gently.

2. Reconstitution (animal)

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

SQ near injury site (preferred), or systemic SQ (abdomen). Rotate sites.

3. Dosing schedule

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

Evening or pre-sleep is most common anecdotal timing.

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.

27–31G, 4–8 mm insulin syringe.

06Stack Synergy

FOXO4-DRI

— no documented stacks

TB-500

+ BPC-157

Strong

View BPC-157 →

TB-500 and BPC-157 cover complementary halves of tissue repair: BPC-157 upregulates VEGFR2-driven angiogenesis and fibroblast outgrowth; TB-500 sequesters G-actin to enable endothelial / epithelial migration. The anecdotal canonical "healing stack" — pairs especially well for tendon and ligament injuries.

TB-500: 2 mg SQ · 2× per week
BPC-157: 250–500 mcg SQ · daily
Primary benefit: Combined angiogenesis + cell migration for tendon/ligament/muscle repair