Research Dossier on TB500

(Reproductive Peptide)

Classification & Molecular Identity

What “TB-500” means in the scientific literature (nomenclature caveat)

“TB-500” is not a standardized scientific name. In retail and grey-market contexts it is typically used to denote either:

1. the full-length thymosin β4 (Tβ4) protein (43 amino acids; encoded by TMSB4X), a ubiquitous actin-monomer–binding peptide; or

2. a short peptide fragment modeled on Tβ4’s actin-binding motif (e.g., LKKTETQ, sometimes N-acetylated) or on the downstream tetrapeptide Ac-SDKP that is enzymatically released from Tβ4 in vivo.

Peer-reviewed publications overwhelmingly study Tβ4 itself, its fragments, or Ac-SDKP; the label “TB-500” rarely appears in scholarly work except in doping control (to detect an N-acetyl-LKKTETQ peptide in equine samples) or quality-control alerts about misbranded Internet products (see safety/quality below). For accuracy, this dossier treats TB-500 as an umbrella for Tβ4 and Tβ4-derived fragments, and it documents explicitly which entity each study examined. PubMed+1

Amino acid sequence, molecular weight, structural motifs

• Thymosin β4 (Tβ4): 43 aa acidic peptide; the canonical actin-binding motif is LKKTET (often extended to LKKTETQ), which sequesters G-actin and regulates cytoskeletal dynamics. Reported molar mass for Tβ4 is ~4.9 kDa; pI is acidic owing to multiple Asp/Glu residues. PubMed+1

• Actin-binding fragment: LKKTETQ (sometimes N-acetylated) has been studied as a minimal activity mimic and is the analytical target in equine doping assays marketed as “TB-500.” PubMed

• Ac-SDKP (N-acetyl-Ser-Asp-Lys-Pro): an endogenous antifibrotic tetrapeptide generated from Tβ4 by meprin-αfollowed by prolyl-oligopeptidase (POP); Ac-SDKP has a distinct and substantial literature in organ fibrosis. Physiology Journals+1

Discovery history (lab, year, species)

• Tβ4 was identified as a major actin-sequestering peptide widely distributed in mammalian cells and body fluids; actin sequestration underlies its roles in cell migration, angiogenesis, wound healing, and tissue repair. PubMed

• Wound repair (1999–2003): Foundational animal studies demonstrated that exogenous Tβ4 accelerates dermalwound healing (topical or intraperitoneal) and that a 7-aa motif (LKKTETQ) can mimic aspects of Tβ4’s reparative activity in aged mice. PubMed+1

• Cornea (2002 onward): Tβ4 promoted corneal re-epithelialization and dampened inflammation in preclinical models, spawning ophthalmic development programs and phase 2–3 trials for dry-eye disease and neurotrophic keratopathy (RGN-259 eye drops). PMC+2MDPI+2

• Ac-SDKP antifibrosis: The Tβ4–POP–Ac-SDKP axis emerged as a conserved antifibrotic pathway with efficacy across heart, kidney, liver, and lung models; mechanistic enzymology of Ac-SDKP release from Tβ4 was clarified in 2016. Physiology Journals+1

Endogenous vs synthetic origin

• Endogenous: Tβ4 is endogenous and abundant; platelets, macrophages, and many cell types release Tβ4 at injury sites. Ac-SDKP is also endogenous, formed from Tβ4 by meprin-α and POP. PubMed+1

• Synthetic: Research-grade Tβ4, LKKTETQ, and Ac-SDKP are produced synthetically for experiments and (for Ac-SDKP) as standards in pharmacology.

Homologs, analogs, derivatives

• Family: Thymosin β family (β4, β10, β15, etc.) share actin-binding capacities.

• Fragments & mimetics: LKKTET/LKKTETQ (actin-binding epitope), Ac-SDKP (antifibrotic fragment), and peptide hydrogels delivering Tβ4 or fragments for tissue repair. PubMed

Historical Development & Research Trajectory

Key milestones

• Dermal repair: Rat and mouse studies (1999–2003) showed accelerated re-epithelialization, increased keratinocyte migration, collagen deposition, and contraction with exogenous Tβ4. Representative investigational doses: topical application (µg per wound) or i.p. injections (1–10 mg·kg⁻¹, model-dependent). PubMed

• Ophthalmology: In cornea, Tβ4 reduced inflammation and accelerated closure after alkali or epithelial injury; these preclinical findings led to clinical trials (e.g., RGN-259), some reporting symptom/sign improvements in dry eye and neurotrophic keratopathy. PMC+1

• Cardiac/vascular: Tβ4 has roles in angiogenesis and vascular development; post-MI and ischemia models reported improved neovascularization and tissue preservation. PubMed

• Neuroprotection: In traumatic brain injury (TBI) models, Tβ4 improved functional recovery, reduced inflammation/apoptosis, and promoted angiogenesis—leading to proposals for neurorestorative therapy. PMC

• Antifibrotic axis (Tβ4→Ac-SDKP): Across lung, kidney, liver, and heart fibrosis models, Ac-SDKP consistently reduced fibrosis; in bleomycin lungs, 0.6 mg·kg⁻¹ i.p. bi-weekly prevented and treated fibrosis (investigational). Oncotarget

Paradigm shifts & controversies

• From actin to antifibrosis: Initially viewed as an actin-sequestering cytoskeletal regulator, Tβ4 is now linked to regeneration and antifibrotic pathways, partly through its Ac-SDKP fragment; mechanistic integration of cell migration, angiogenesis, inflammation, and matrix remodeling remains under study. PubMed

• TB-500 product ambiguity: Analyses of Internet-sold “TB-500/TB-1000/SGF-1000” found misbranding/adulteration and unapproved compositions, underscoring the gap between biomedical literature(Tβ4/fragments) and commercial “TB-500” offerings. PubMed

• Species/route translation: Strong animal data (dermis, cornea, heart, lung) do not automatically predict human therapeutic outcomes; rigorous, indication-specific phase 3 clinical validation is still limited to ophthalmicprograms.

Evolution of scientific interest

Work has expanded from wound closure → angiogenesis → neurorepair → antifibrosis (Ac-SDKP) → anti-aging/regenerative directions leveraging developmental programs. PMC

Mechanisms of Action

Primary and secondary interactions

• Actin sequestration & cell migration (Tβ4): Tβ4 binds G-actin via its LKKTET motif, regulating filament dynamics that drive cell motility—a central mechanism for keratinocyte and endothelial migration during repair. PubMed

• Angiogenesis: Tβ4 promotes endothelial cell migration/tube formation and VEGF-dependent neovascularization in injured tissues; this underlies dermal and cardiac repair effects. PubMed+1

• Anti-inflammatory/anti-apoptotic: After injury, Tβ4 released by platelets/macrophages reduces apoptosis and inflammation and can modulate microbial growth; corneal studies emphasize inflammatory dampening plus re-epithelialization. PubMed+1

• Antifibrosis (Ac-SDKP): The Tβ4→POP→Ac-SDKP axis suppresses TGF-β/Smad-linked fibroblast activation, reduces collagen deposition, and in some models reverses established fibrosis in lung, kidney, liver, heart. PMC+2PMC+2

• Neurorestoration: In TBI models, Tβ4 attenuates inflammation/apoptosis, enhances angiogenesis, and supports neurogenesis/oligodendrogenesis, improving functional outcomes. PMC

Synthesis: Tβ4 acts as a multifunctional regulator that (i) remodels the cytoskeleton for migration, (ii) promotes angiogenesis, (iii) restrains inflammation/apoptosis, and (iv) via Ac-SDKP, counteracts fibrosis. These effects combine to accelerate repair and limit scarring across tissues.

Intracellular signaling pathways (selected/inferred)

• Actin/ILK/FAK: Tβ4’s cytoskeletal effects interface with integrin-linked kinase (ILK) and focal adhesion kinase (FAK); downstream are ERK, PI3K/AKT, and Rho GTPases controlling lamellipodia/filopodia in migrating cells (inferred from endothelial/keratinocyte studies). PubMed

• VEGF/angiogenic: Up-regulation of VEGF and proangiogenic cytokines; enhanced endothelial survival and tube formation. PubMed

• TGF-β/Smad modulation (Ac-SDKP): Down-tunes pro-fibrotic transcriptional programs; promotes MMP activity and balanced remodeling in fibrotic organs. PMC

• Inflammatory mediators: Reduced NF-κB activation and cytokines reported in several models (cornea, lung, liver), consistent with anti-inflammatory phenotypes. PMC

CNS vs peripheral effects

• Peripheral: Strongest evidence exists in skin, cornea, cardiovascular system, and fibrotic organs (via Ac-SDKP).

• CNS: TBI studies demonstrate neurorestorative effects in rodents; translation to controlled human neurotrauma trials is Not established. PMC

Hormonal, metabolic, immune interactions

• Tβ4 is released by platelets/macrophages following injury, implicating innate immune-repair crosstalk. It modulates inflammatory and apoptotic pathways and supports angiogenesis, which together shape the local metabolic and oxygenation microenvironment. PubMed

Evidence grading (A–C)

• A (replicated in multiple tissues/models): Dermal and corneal wound-healing acceleration; angiogenesis; anti-inflammation; Ac-SDKP antifibrosis across several organ models. PubMed+2PMC+2

• B (translational/clinical-adjacent): Ophthalmic phase 2–3 programs (RGN-259) for dry-eye and neurotrophic keratopathy; TBI neurorestorative signals in animals; cardiac/vascular preclinical data. PMC+1

• C (uncertain/controversial): Systemic human PK/PD, dosing for non-ophthalmic indications, long-term outcomes, and direct clinical evidence for commercial “TB-500” products—Not established. PubMed

Pharmacokinetics & Stability

ADME profile

• Thymosin β4 (43 aa): As a small acidic protein, Tβ4 is expected to have rapid systemic clearance if administered parenterally; tissue-retention at injury sites may be enhanced via matrix and cellular uptake. Formal human PKfor systemic Tβ4 is not well characterized in peer-reviewed publications. Status: Not established.

• Topical ophthalmic: RGN-259 (Tβ4 eye drops) trials imply local ocular exposure with minimal systemic absorption (class expectation for topical ophthalmics), but quantitative human PK is typically not reported in the published summaries. Status: Not established. MDPI

• Ac-SDKP: Endogenous plasma levels are measurable; it is hydrolyzed by angiotensin-converting enzyme (ACE). Exogenous Ac-SDKP pharmacology is better defined in animal fibrosis models than in humans. PMC

Plasma half-life & degradation pathways

• Tβ4: Rapid proteolysis and renal clearance are expected; half-life in vivo in humans Unknown/Not established.

• Ac-SDKP: Cleared by ACE; pharmacodynamics often tracked by fibrosis biomarkers rather than classical PK. PMC

Stability in vitro & in vivo

• Tβ4 is stable for short experimental windows and is typically formulated in buffered aqueous solutions; hydrogelmatrices can prolong local exposure in wounds. PubMed

• Quality caveat: Independent analyses have documented variable composition/adulteration of commercial “TB-500” products, emphasizing the need for analytical verification (HPLC/MS) when used in research. PubMed

Storage/reconstitution considerations

Peer-reviewed, product-specific CMC is not broadly published; follow vendor Certificates of Analysis for research-usepeptide stability and storage.

Preclinical Evidence

Dermal wound healing

• Rat full-thickness wounds: Tβ4 (topical or i.p.) increased re-epithelialization by ~42% at day 4 and ~61% at day 7, and enhanced contraction by ≥11% at day 7 vs saline. Investigational dosing used in study: topical µg/wound or i.p. mg·kg⁻¹; Malinda 1999. PubMed

• Aged mice: Hydrogel Tβ4 and the 7-mer LKKTETQ accelerated closure, keratinocyte migration, and collagen deposition, approximating parent protein effects. Investigational doses used in study: see Philp 2003. PubMed

Corneal wound healing & ocular surface disease

• Alkali or epithelial injury: Tβ4 reduced inflammation, accelerated re-epithelialization, and improved corneal clarity vs controls. Investigational dosing used in study: topical ophthalmic solutions (concentrations in % range per protocol). PMC

• Ophthalmic translation: Reviews summarize RGN-259 (0.1% Tβ4) outcomes in dry-eye disease and neurotrophic keratopathy with favorable safety; ongoing/complete phase 2–3 trials are documented in the ophthalmic literature and registries (see Human Clinical Evidence). MDPI+1

Cardiovascular & vascular development

• Angiogenesis and vascular protection: Tβ4 has recognized roles in vascular development, neovascularization, and protection against vascular disease; several MI/ischemia models demonstrate enhanced neovessel formationand improved tissue outcomes. Investigational routes/doses vary (local/systemic). PubMed

CNS and neurorestoration

• Traumatic brain injury (TBI): Tβ4 improved sensorimotor and cognitive recovery, reduced apoptosis/inflammation, and promoted angiogenesis and cell survival in rat models. Investigational dosing used in study: typically 1.6–6 mg·kg⁻¹ i.p. or local over multiple days; see Xiong 2012. PMC

Antifibrotic biology (Ac-SDKP)

• Liver: Ac-SDKP reduced experimental liver fibrosis in multiple models (CCl₄, choline-deficient diet) via anti-inflammatory/antifibrotic signaling. PMC

• Kidney: In renal fibrosis, Ac-SDKP lowered collagen and attenuated inflammation; it is released from Tβ4 by meprin-α → POP, and degraded by ACE—linking the axis to RAAS biology. Physiology Journals

• Lung: In bleomycin fibrosis, Ac-SDKP 0.6 mg·kg⁻¹ i.p., given on the day of injury and twice weekly, preventedfibrosis; therapeutic dosing initiated at day 7 reduced established fibrosis. Investigational doses used in study Conte 2016. Oncotarget

• Heart: The antifibrotic axis is implicated in cardiac remodeling and scar attenuation, with ongoing interest in dosing strategies to leverage Tβ4–POP–Ac-SDKP for organ protection. MDPI

Dose ranges tested (illustrative; all investigational)

• Dermal wounds: topical Tβ4 (µg per wound) or 1–10 mg·kg⁻¹ i.p. in early studies. PubMed

• Ocular: topical 0.1% ophthalmic solution (e.g., RGN-259) in clinical protocols. MDPI

• TBI: ~1.6–6 mg·kg⁻¹ i.p. repeated dosing (model-specific). PMC

• Lung fibrosis (Ac-SDKP): 0.6 mg·kg⁻¹ i.p., bi-weekly preventive/therapeutic. Oncotarget

Comparative efficacy/safety (preclinical)

• Efficacy: Strong, consistent reparative signals (dermis/cornea), angiogenesis, anti-inflammation, and antifibrosis(Ac-SDKP).

• Safety: Animal studies report good tolerability at investigational doses; for systemic Tβ4 human safety/PK remain Not established.

Limitations

• Variability in formulation (solution vs hydrogel), route, and injury model complicate standardization.

• The label “TB-500” used in commerce often does not map cleanly to peer-reviewed Tβ4 reagents. PubMed

Human Clinical Evidence

Ophthalmology

• Dry eye disease (DED) and neurotrophic keratopathy (NK): 0.1% Tβ4 (RGN-259) eye drops have been evaluated in phase 2–3 studies. Reviews and trial summaries report improvements in prespecified signs/symptoms and favorable safety profiles; detailed results vary by study and endpoint. Investigational regimen used in study: topical 0.1% solution, multiple times daily over several weeks (trial-specific). PMC+1

• ClinicalTrials.gov lists completed ophthalmic studies (e.g., NCT01387347); postings summarize safety/efficacy outcomes for NK and DED with RGN-259. ClinicalTrials.gov

Dermatology/orthopedics (human data)

• Peer-reviewed randomized trials outside ophthalmology are sparse. Case series and early-phase studies have suggested benefit in chronic dermal wounds and tendon contexts, but controlled, adequately powered trials are limited in the indexed literature. Status: Not established.

Neuro/CV

• For TBI or post-MI, no large randomized human trials of Tβ4 are published in mainstream journals to date; evidence remains preclinical or early clinical (exploratory). Status: Not established. PMC

Dosing examples (human, investigational, indication-specific)

• Ocular (RGN-259): 0.1% ophthalmic solution, QID–6×/day over 4–8 weeks, per trial protocol (DED/NK). Investigational dose used in study. MDPI

Safety signals/adverse events (human)

• Ophthalmic: Generally well tolerated; common AEs are mild, localized (e.g., transient irritation). Systemic AEs uncommon given topical route. MDPI

• Systemic Tβ4: Human PK/PD and long-term safety for parenteral administration are Not established in peer-reviewed literature.

ClinicalTrials.gov IDs (examples)

• NCT01387347 (Tβ4 ophthalmic; safety/efficacy in corneal indications). ClinicalTrials.gov

• Additional phase-2/3 ophthalmic studies of RGN-259 are catalogued in sponsor and registry postings summarized in reviews. PMC

Comparative Context

Related peptides/approaches

• VEGF/FGF-based angiogenic therapies (pro-angiogenic), MMP modulators, and anti-TGF-β agents for fibrosis overlap mechanistically with Tβ4/Ac-SDKP axes.

• Other actin-binding proteins lack the small, drug-like peptide footprint of Tβ4; short mimetics (LKKTETQ, Ac-SDKP) offer modularity for targeted delivery.

Advantages (research perspective)

• Endogenous biology with multifunctional repair actions (migration + angiogenesis + anti-inflammation + antifibrosis) supported across tissues.

• Fragment pharmacology (Ac-SDKP) provides a defined antifibrotic axis with mechanistic clarity (POP & ACE regulation). Physiology Journals

Disadvantages/constraints

• Human systemic PK/PD and dose-finding remain unclear outside ophthalmology.

• Commercial “TB-500” quality is highly variable; misbranding/adulteration documented. PubMed

• Translation risk: Not all animal successes translate to human phase-3 outcomes; indication-specific optimization is required.

Research category placement

Tβ4/Ac-SDKP research spans tissue repair, angiogenesis, fibrosis, and neurorestoration—with an established niche in ophthalmology and expanding interest in organ antifibrosis.

Research Highlights

• Dermal & corneal wound healing: Accelerated closure, re-epithelialization, and improved matrix remodeling; corneal trials reached phase 3 with RGN-259. PubMed+1

• Angiogenesis: Tβ4 supports endothelial migration and tube formation; implicated in vascular development and post-ischemic neovascularization. PubMed

• Neurorepair (TBI): Benefits in functional recovery, anti-apoptosis, and angiogenesis, motivating neurorestorative exploration. PMC

• Antifibrosis (Ac-SDKP): Prevents and reverses fibrosis in lung/kidney/liver/heart models; enzymology links Tβ4 cleavage to meprin-α/POP, with ACE as a clearance point. PMC+1

• Quality caution: “TB-500” marketed products may be misbranded/adulterated; scientific studies generally employ validated Tβ4 or Ac-SDKP reagents. PubMed

Conflicting/uncertain areas.

• Optimal systemic dosing, exposure–response, and long-term safety in humans: Not established.

• Direct clinical evidence for non-ophthalmic indications remains heterogeneous.

Potential Research Applications (no clinical claims; research-use framing)

1. Actin-driven cell migration

   • Quantify FAK/ILK and Rho GTPase dynamics in keratinocyte and endothelial wound models under Tβ4 vs LKKTETQ, with live-cell imaging of lamellipodia and traction forces. PubMed

2. Angiogenesis and matrix remodeling

   • Combine 3D collagen gels and microfluidic vasculature with Tβ4 to dissect sprouting, pericyte recruitment, MMP activity, and VEGF-dependent signatures. PubMed

3. Corneal epithelialization & neurotrophic keratopathy

   • Map nerve–epithelium cross-talk using human corneal organoids; integrate single-cell RNA-seq to define inflammatory vs repair modules modulated by Tβ4. PMC

4. Antifibrotic Tβ4→Ac-SDKP axis

   • In liver/kidney/lung/heart fibrosis models, quantify TGF-β/Smad signaling, collagen cross-linking, and MMP/TIMP balance under Ac-SDKP; manipulate POP/ACE to validate axis control points. PMC

5. Neurorestoration

   • In TBI or stroke models, test Tβ4 timing/route (local vs systemic) on angiogenesis, oligodendrogenesis, and axon sprouting; pair with behavioral batteries and diffusion MRI. PMC

6. Quality & analytics for “TB-500”

   • Apply LC-MS/MS and peptide mapping to characterize commercial materials; benchmark against reference Tβ4/Ac-SDKP; evaluate bioactivity (cell migration, actin dynamics) to ensure scientific reproducibility. PubMed

Safety & Toxicology

Preclinical

• Tβ4 and Ac-SDKP show favorable tolerability in standard animal models at research doses; no major toxicity signals are consistently reported across dermal, ocular, and organ-fibrosis studies. Nevertheless, classic GLPrepeat-dose, reproductive, and carcinogenicity packages for systemic Tβ4 are not comprehensively available in the public domain. Status: Not established.

Human

• Ophthalmic Tβ4 (RGN-259): Trials report good local tolerability and few systemic AEs, consistent with minimal systemic absorption. MDPI

• Systemic Tβ4 (parenteral): Human PK/safety are not well defined in peer-reviewed sources, and unregulated “TB-500” products have raised safety concerns (misbranding/adulteration). Status: Unknown/Not established. PubMed

Specific risks/considerations

• Pro-angiogenic signaling is beneficial in repair but warrants oncology/neovascular surveillance in chronic dosing contexts (theoretical risk; human evidence insufficient).

• Antifibrotic axis intersects ACE/RAAS; interactions with ACE inhibitors are plausible and merit study (Ac-SDKP is ACE-degraded). PMC

• Quality: Non-compliant “TB-500” products may contain incorrect sequences, contaminants, or adulterants. PubMed

Limitations & Controversies

• Terminology: “TB-500” ≠ single, validated molecular entity; peer-reviewed data pertain to Tβ4, LKKTETQ, or Ac-SDKP. PubMed

• PK knowledge gap: Human systemic PK/PD for Tβ4 is limited; exposure–response modeling is Not established.

• Clinical translation: Outside ophthalmology, controlled human trials are limited; animal successes require indication-specific, randomized human validation.

• Product quality: Documented misbranding/adulteration of Internet “TB-500” undermines reproducibility and safety. PubMed

Future Directions

1. Define exposure: Conduct first-principles PK/PD for systemic Tβ4 and Ac-SDKP (including bioavailability, t½, tissue distribution), and validate biomarkers (e.g., circulating Ac-SDKP, collagen neo-epitopes).

2. Mechanistic mapping: Decouple actin-dependent migration vs anti-inflammatory and antifibrotic actions using loss-of-function (e.g., POP/ACE manipulation) and single-cell multi-omics. Physiology Journals

3. Indication-focused RCTs: In corneal disease, pursue larger phase-3 trials with standardized endpoints; in fibrosis, design translational trials leveraging Ac-SDKP PD and imaging (MRI-PDFF, elastography). MDPI

4. Delivery: Evaluate localized depots (hydrogels, matrices) to maximize tissue exposure while minimizing systemic risk. PubMed

5. Quality frameworks: Standardize analytical criteria (identity, purity, potency, contaminants) for any TB-500-labeled research materials to align commercial supplies with scientific Tβ4/Ac-SDKP standards. PubMed

References

1. Goldstein AL, et al. Thymosin β4: a multi-functional regenerative peptide. Basic Res Cardiol. 2012. PMID: 22074294. (Overview of Tβ4 biology in repair/regeneration.) PubMed

2. Malinda KM, et al. Thymosin β4 accelerates wound healing. J Invest Dermatol. 1999. PMID: 10469335. (Dermal re-epithelialization & contraction; rat model.) PubMed

3. Philp D, et al. Tβ4 and a synthetic peptide containing its actin-binding domain accelerate wound healing in aged mice. FASEB J. 2003. PMID: 12581423. (Hydrogel delivery; LKKTETQ mimetic.) PubMed

4. Sosne G, et al. Tβ4: corneal wound-healing & anti-inflammatory peptide. Ocul Surf. 2007; PMCID: PMC2701135. (Corneal re-epithelialization; inflammation.) PMC

5. Sosne G, et al. 0.1% RGN-259 (Tβ4) ophthalmic solution: translational overview. Int J Mol Sci. 2022. (Ophthalmic clinical program summary.) MDPI

6. Sosne G, et al. Thymosin β4: potential novel adjunct therapy in ophthalmology. Pharmacol Ther. 2023. (Review; DED/NK trials.) ScienceDirect

7. Dubé KN, et al. Tβ4 & the vasculature: roles in development & disease. Vascul Pharmacol. 2018. PMID: 30063849. PubMed

8. Xiong Y, et al. Neuroprotective/neurorestorative effects of Tβ4 in TBI. J Neurosci Res. 2012; PMCID: PMC3547647. PMC

9. Kumar N, et al. Ac-SDKP is released from Tβ4 by meprin-α and POP. Am J Physiol Renal Physiol. 2016. (Enzymology of Tβ4→Ac-SDKP.) Physiology Journals

10. Conte E, et al. Preventive & therapeutic effects of Ac-SDKP in pulmonary fibrosis. Oncotarget. 2016; PMCID: PMC5085123. (Bleomycin model; dosing schedules.) PMC

11. Kassem KM, et al. Tβ4–Ac-SDKP pathway in fibrosis & inflammation (review). Cells. 2019; PMCID: PMC6824425. PMC

12. Kleinman HK, et al. Tβ4 and the anti-fibrotic switch. Pharmacol Res. 2023. (Perspective on Ac-SDKP reversing fibrosis.) ScienceDirect

13. Ying Y, et al. Tβ4 and actin: binding modes, biological functions & disease roles. Int J Biol Macromol. 2023. PMID: 36464872. (Comprehensive actin-binding review.) PubMed

14. Ho ENM, et al. Doping control analysis of “TB-500” (N-acetyl-LKKTETQ) & metabolites in equine samples.Rapid Commun Mass Spectrom. 2012. PMID: 23084823. PubMed

15. Delcourt V, et al. “TB-500/TB-1000/SGF-1000”: misbranded & adulterated Internet products. Clin Chim Acta.2023. PMID: 36482504. (Quality/safety alert.) PubMed

16. Xing Y, et al. Progress on the function and application of Tβ4. Front Endocrinol. 2021; PMCID: PMC8724243. (Domain-spanning review; clinical perspectives.) PMC

Representative investigational amounts (study-specific):
• Dermal wound (rat): topical Tβ4 (µg/wound) or 1–10 mg·kg⁻¹ i.p. accelerated closure and contraction (Malinda 1999). PubMed
• Aged mouse skin: hydrogel Tβ4 and LKKTETQ mimetic improved closure (Philp 2003). PubMed
• Ocular surface (human trials): topical 0.1% ophthalmic solution (RGN-259) QID–6×/day for 4–8 weeks, indication-specific (Sosne 2022; ClinicalTrials.gov NCT01387347). MDPI+1
• Pulmonary fibrosis (mouse): Ac-SDKP 0.6 mg·kg⁻¹ i.p. on day 0 and twice weekly prevented fibrosis; starting day 7 reduced established fibrosis (Conte 2016). Oncotarget
• TBI (rat): repeated 1.6–6 mg·kg⁻¹ i.p. improved functional recovery and angiogenesis (Xiong 2012). PMC

⚠️ Disclaimer This peptide is intended strictly for laboratory research use. It is not FDA-approved or authorized for human use, consumption, or therapeutic application.