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TB-500

TB-500

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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

  1. 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).

  2. 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).

  3. 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).

  4. 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).

  5. 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).

  6. 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

Protocols Using This Peptide

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

Related

#peptide #recovery #anti-aging #cosmetic #subq #iv #topical