TB-500

Synthetic fragment of Thymosin Beta-4; G-actin sequestration peptide promoting cell migration, angiogenesis, and anti-fibrotic tissue repair

Quick Facts

Property	Value
Also Known As	Thymosin Beta-4 fragment, Tβ4, Ac-LKKTETQ
Category	Recovery / Anti-Aging / Wound Healing
Sequence	Ac-LKKTETQ (7 amino acids; active fragment of 43-aa Thymosin Beta-4)
Molecular Weight	~889 Da (fragment); ~4963.5 Da (full-length Tβ4)
Molecular Formula	C₃₈H₆₇N₉O₁₃ (fragment)
PubChem CID	16132341
Administration	SubQ / IV / Topical
Typical Dose Range	2.0–2.5 mg SubQ 2x/week (loading), 1x/week-biweekly (maintenance)
Half-Life	~2–3 hours (plasma)
Storage	Lyophilized: -20°C, stable 24 months; Reconstituted: 2–8°C, use within 14–28 days
FDA Status	Research-only; not FDA-approved; reclassified as biologic. RGN-259 (Tβ4 eye drops) advanced to Phase 3 for dry eye/neurotrophic keratopathy
WADA Status	Prohibited under S0 (Non-Approved Substances)

Mechanism of Action

TB-500 is the active fragment of Thymosin Beta-4 (Tβ4), the most abundant beta-thymosin in human cells, comprising 70-80% of all beta-thymosins. Its primary mechanism is G-actin sequestration via the WH2 domain, maintaining a ready pool of unpolymerized actin monomers for rapid filament assembly during cell migration. This drives fibroblast, keratinocyte, and endothelial cell movement to injury sites via filopodia and lamellipodia formation (PMID-36464872).

TB-500 activates the ILK-PINCH-Akt survival pathway, providing anti-apoptotic signaling through Caspase-3 inhibition. This is the key mechanism for cardioprotection — Tβ4 reduces infarct volume, prevents cardiac rupture post-MI, and preserves left ventricular function. It also activates epicardial progenitor cells, recapitulating developmental cardiac repair programs (PMID-25015963, PMID-27450736).

TB-500 stabilizes HIF-1α under normoxic conditions, upregulating VEGF and promoting angiogenesis independently of hypoxia. It also inhibits NF-κB, suppressing TNF-α, IL-1β, and IL-8 inflammatory cascades. Its metabolite Ac-SDKP exerts anti-fibrotic effects by inhibiting TGF-β signaling and preventing myofibroblast differentiation, reducing scar formation during healing (PMID-34992578).

Tβ4 operates through multiple signaling pathways including NF-κB, PI3K/Akt/eNOS, Notch, TGF-β, and Wnt pathways, making it one of the most multi-modal tissue repair peptides known. It also promotes hair follicle stem cell migration and differentiation, establishing a direct role in hair growth biology (PMID-17947589).

Key Research Areas

Wound Healing — The foundational Malinda et al. (1999) study demonstrated topical Tβ4 increased re-epithelialization by 42-61% in rat dermal wounds, with enhanced angiogenesis and collagen deposition (PMID-10469335). Corneal wound healing and anti-inflammatory properties are well documented (PMID-19668473).
Cardiac Repair — Peng et al. (2014) showed Tβ4 prevents cardiac rupture and improves cardiac function post-MI in mice, with reduced inflammation, decreased infarct size, and enhanced capillary density (PMID-25015963). Pipes (2016) reviewed the full cardioprotective evidence including epicardial progenitor cell activation (PMID-27450736).
Ocular Applications (Clinical Trials) — RGN-259 (Tβ4 eye drops) advanced to Phase 3 clinical trials for dry eye and neurotrophic keratopathy, representing the most advanced clinical development of any Tβ4 formulation (PMID-30063853).
Hair Growth — Philp et al. (2007) demonstrated Tβ4 promotes hair growth in rodent models by stimulating hair follicle stem cell migration from the bulge region (PMID-17947589).
Anti-Aging and Regeneration — Bock-Marquette et al. (2023) reviewed Tβ4's potential as an anti-aging regenerative therapy, proposing that postnatal administration of developmental peptides may reverse aging processes (PMID-36709593).
Anti-Infection — Tβ4 participates in antibacterial immunity across multiple species and tissue types (PMID-37018981, PMID-37689229).

Evidence Level Summary

Evidence Type	Count	Notes
Human clinical trials	0 direct	Phase 3 trials for RGN-259 (Tβ4 eye drops) reviewed in PMID-30063853
Animal in vivo	5	Wound healing, cardiac repair, hair growth, antibacterial
In vitro	0	—
Narrative reviews	8	Mechanism, cardiac, ocular, anti-aging, functions overview
Total vault studies	13

The evidence base for TB-500 is extensive preclinically but limited clinically. No human RCTs exist for systemic TB-500 injection. The closest clinical data comes from Phase 2/3 trials of RGN-259 (topical Tβ4 eye drops) for ophthalmological indications. Phase 1 IV safety data showed no drug-related serious adverse events at doses up to 1260 mg. Cardiac repair and wound healing data is robust in animal models across multiple research groups (not single-group dependent).

Clinical Applications

Tendon and Ligament Repair — Promotes cell migration and collagen remodeling at injury sites
Muscle Tears — Actin-mediated cell migration and anti-fibrotic healing
Wound Healing — 42-61% improvement in re-epithelialization in preclinical models
Injury Recovery — Broad musculoskeletal healing via systemic cell recruitment
Stroke Recovery — Neuroprotective and angiogenic properties (preclinical)
Post-Procedure Recovery — Anti-inflammatory and anti-scarring properties
Hair Growth — Stem cell migration and differentiation in hair follicles
Autoimmune Conditions — NF-κB inhibition and anti-inflammatory cascade
Cardiac Health — Cardioprotection, infarct reduction, epicardial progenitor activation

Protocols Using This Peptide

Wolverine Stack Protocol — Core peptide (paired with BPC-157 and MGF)
Recovery Stack Protocol — Core systemic recovery peptide
Post-Stroke Recovery Protocol — Adjunct for neuroprotection and angiogenesis

Ageless Peps Products

AP-TB500-Vial — TB-500 Vial, variable sizes, $65 retail (currently out of stock)
AP-TB500-500MCG-Capsules — TB-500 Capsules, 500mcg x 60 caps, $164 retail
AP-BPC157-TB500-Blend — BPC-157/TB-500 Blend Vial, from $65 retail
AP-WOLVERINE-Blend — WOLVERINE Blend (BPC-157 + TB-500 + MGF), $109 retail
AP-GLOW-Blend — GLOW Blend (GHK-Cu + TB-500 + BPC-157), from $134 retail
AP-KLOW-Blend — KLOW Blend (GHK-Cu + TB-500 + BPC-157 + KPV), $153 retail
AP-BPC157-TB500-Capsules — BPC-157/TB-500 Capsules, $284 retail
AP-Sample-Pack — Sample Pack (GLP-3 + BPC-157 + TB-500), $165 retail

Dosing Reference

Research Dosing Ranges

Route	Dose Range	Frequency	Duration	Source
SubQ	2.0–2.5 mg	2x/week (loading)	4–6 weeks	Practitioner guides
SubQ	2.0–2.5 mg	1x/week-biweekly (maintenance)	Ongoing	Practitioner guides
IV	Up to 1260 mg (Phase 1 safety)	Single dose	Phase 1 only	Phase 1 safety data
Topical (eye drops)	RGN-259 formulation	Multiple daily	Phase 3 trials	PMID-30063853 – Thymosin beta 4 and the eye bench to bedside

Cycling

Standard cycling: 6 weeks on, 4 weeks off. Loading at 2x/week transitioning to maintenance at 1x/week or biweekly. No formal cycling protocol in peer-reviewed literature; guidance from practitioner consensus.

Contraindications & Safety

Contraindications: Active malignancy (absolute — TB-500 promotes epithelial-mesenchymal transition which can facilitate metastasis). Proliferative retinopathy (risk of pathological neovascularization). Concurrent chemotherapy (protects cancer cells from apoptosis via Akt pathway).
Common side effects: Mild injection site reactions, transient lethargy, headaches
Drug interactions: Theoretical interaction with chemotherapeutic agents (anti-apoptotic effect may reduce efficacy). Caution with anticoagulants (angiogenesis promotion).
Pregnancy/nursing: Not recommended; no safety data
Special populations: Phase 1 IV safety: no drug-related serious adverse events at doses up to 1260 mg IV. No systematic data on renal, hepatic, or geriatric populations.

Safety profile based on Phase 1 IV data and extensive preclinical use. No completed Phase 2/3 systemic safety trials. RGN-259 Phase 3 trials (topical ocular) provide the most advanced clinical safety data for Tβ4.

Cancer Considerations

CONTRAINDICATED in active malignancy. TB-500 promotes epithelial-mesenchymal transition (EMT) which can facilitate metastasis, and protects cells from apoptosis via the ILK-PINCH-Akt pathway — which may inadvertently protect cancer cells from programmed death. Both mechanisms make TB-500 dangerous in cancer contexts. See Compliance / Cancer Safety Matrix for full ratings.

Synergistic Combinations

BPC-157 + TB-500 — Complementary dual-mechanism: BPC-157 drives local angiogenesis while TB-500 provides systemic cell migration. Used in Wolverine Stack Protocol
GHK-Cu + TB-500 — Multi-peptide healing: GHK-Cu adds copper-dependent collagen remodeling. Used in GLOW blend
KPV + TB-500 — Anti-inflammatory synergy: KPV provides melanocortin NF-κB suppression. Used in KLOW blend
PEG-MGF + TB-500 — Muscle repair: MGF activates satellite cells while TB-500 provides cell migration. Used in WOLVERINE blend

Related Research

PMID	Title	Year	Study Type
PMID-10469335	Thymosin beta4 accelerates wound healing	1999	Animal in vivo
PMID-17468232	beta-Thymosins: small acidic peptides with multiple functions	2007	Narrative Review
PMID-17947589	Tβ4 induces hair growth via stem cell migration	2007	Animal in vivo
PMID-19668473	Tβ4: corneal wound healing and anti-inflammatory agent	2009	Narrative Review
PMID-25015963	Tβ4 prevents cardiac rupture post-MI	2014	Animal in vivo
PMID-27450736	Cardioprotection by Thymosin Beta 4	2016	Narrative Review
PMID-30063853	Tβ4 and the eye: bench to bedside (Phase 3 trials)	2018	Narrative Review
PMID-34992578	Progress on Function and Application of Tβ4	2021	Narrative Review
PMID-36464872	Tβ4 and Actin: Binding Modes, Functions, Applications	2023	Narrative Review
PMID-36709593	Tβ4: anti-aging regenerative therapies	2023	Narrative Review
PMID-37018981	Tβ4: adjunct treatment for bacterial infections	2023	Narrative Review
PMID-37689229	Tβ4 in antibacterial immunity and wound healing	2023	Animal in vivo
PMID-38706788	Tβ4: healing middle ear lesions	2024	Narrative Review

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