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phase 2Tissue Repair & Healing

TB-4 Fragment (Ac-SDKP)

Also known as: Ac-SDKP, N-Acetyl-Ser-Asp-Lys-Pro, Thymosin Beta-4 Fragment 1-4, Goralatide, Seraspenide

TB-4 Fragment, known as Ac-SDKP (N-acetyl-seryl-aspartyl-lysyl-proline), is a naturally occurring tetrapeptide derived from the N-terminal region of Thymosin Beta-4. It is released by enzymatic cleavage via prolyl oligopeptidase (POP) and degraded by angiotensin-converting enzyme (ACE). Ac-SDKP has potent anti-fibrotic and anti-inflammatory properties, making it a candidate for treating cardiac fibrosis, renal fibrosis, and inflammatory conditions. ACE inhibitor drugs indirectly raise Ac-SDKP levels, which may contribute to their cardioprotective effects.

3 cited references·6 researched benefits

Quick Answer

TB-4 Fragment (Ac-SDKP) is a tetrapeptide naturally cleaved from Thymosin Beta-4 with potent anti-fibrotic properties. It inhibits collagen deposition by cardiac and renal fibroblasts, reduces inflammation, and regulates hematopoietic stem cell proliferation. Ac-SDKP is naturally degraded by ACE, so ACE inhibitor drugs raise its levels — which may explain part of their organ-protective effects. Phase 2 research explores it for cardiac fibrosis, kidney fibrosis, and inflammatory tissue damage.

Key Facts

Mechanism
Ac-SDKP is cleaved from Thymosin Beta-4 by prolyl oligopeptidase (POP) and normally degraded by angiotensin-converting enzyme (ACE). It exerts anti-fibrotic effects by inhibiting TGF-β/Smad signaling in fibroblasts, preventing their differentiation into myofibroblasts and reducing collagen I and III deposition. Ac-SDKP also inhibits macrophage infiltration and inflammatory cytokine release, blocks endothelial-to-mesenchymal transition (EndMT), and acts as a negative regulator of hematopoietic stem cell entry into S-phase, preventing their premature depletion during chemotherapy or inflammation.
Research Status
phase 2
Half-Life
~4.5 minutes
Molecular Formula
C₁₈H₂₈N₄O₉
Primary Use
Tissue Repair & Healing
Table of Contents

Benefits

  • Potent anti-fibrotic activity — inhibits cardiac and renal collagen depositionstrong
  • Anti-inflammatory — reduces macrophage infiltration and inflammatory cytokine productionstrong
  • Hematopoietic stem cell protection — prevents premature stem cell depletion during stressmoderate
  • Cardioprotection — reduces cardiac fibrosis and improves heart function post-MI in animal modelsmoderate
  • Renal protection — attenuates kidney fibrosis in chronic kidney disease modelsmoderate
  • May mediate organ-protective effects of ACE inhibitor therapypreliminary

Dosage Protocols

RouteDosage RangeFrequencyNotes
Subcutaneous injection (investigational)100–500 mcgDaily (due to very short half-life)Extremely short plasma half-life (~4.5 minutes) due to rapid ACE degradation. Sustained-release formulations or osmotic pumps used in preclinical studies.
Continuous infusion (preclinical)400–800 mcg/kg/dayContinuous via osmotic minipumpMost preclinical anti-fibrosis studies use continuous infusion to overcome the very short half-life.

Medical disclaimer

Dosage information is provided for educational reference only. Always follow your prescriber's instructions and consult a qualified healthcare provider before starting any peptide protocol.

Side Effects

  • Injection site irritationcommon
  • Transient hypotension (due to anti-fibrotic vasodilatory mechanisms)rare
  • Headacherare
  • Theoretical risk of impaired wound healing with excessive anti-fibrotic activityserious

Frequently Asked Questions

What is the relationship between TB-4 Fragment (Ac-SDKP) and TB-500?
Ac-SDKP is a tetrapeptide (4 amino acids) that is naturally cleaved from the N-terminal end of Thymosin Beta-4, the full-length 43-amino acid peptide that TB-500 is based on. While TB-500 promotes tissue repair through actin regulation and cell migration, Ac-SDKP specifically targets anti-fibrotic and anti-inflammatory pathways. They have complementary but distinct mechanisms — TB-500 builds new tissue while Ac-SDKP prevents excessive scarring.
Why do ACE inhibitors raise Ac-SDKP levels?
ACE (angiotensin-converting enzyme) is the primary enzyme that degrades Ac-SDKP in the body. When patients take ACE inhibitors like lisinopril or enalapril, they block ACE activity, which prevents Ac-SDKP breakdown and causes its plasma levels to rise approximately 5-fold. This elevation of Ac-SDKP is now thought to be one of the mechanisms by which ACE inhibitors provide cardiac and renal protection beyond their blood pressure-lowering effects.
Can Ac-SDKP be used clinically for fibrosis?
Currently, Ac-SDKP is in the preclinical and phase 2 research stage for fibrotic conditions. Its extremely short half-life (~4.5 minutes) makes direct clinical use challenging without sustained-release formulations. However, the discovery that ACE inhibitors raise endogenous Ac-SDKP levels has led to the concept that some of the organ-protective benefits patients already receive from ACE inhibitor therapy may be mediated through this peptide. Direct Ac-SDKP therapy would require novel delivery systems to be clinically practical.

References

  1. 1
    N-acetyl-Ser-Asp-Lys-Pro: a potent natural inhibitor of hematopoietic stem cell entry into S-phase(2003)PubMed ↗
  2. 2
    Ac-SDKP: a novel anti-fibrotic peptide — role in cardiac and renal fibrosis(2015)PubMed ↗
  3. 3
    Thymosin beta-4 and Ac-SDKP in cardiovascular protection and repair(2012)PubMed ↗

Latest Research

Last updated: 2026-02-19