Ac-SDKP
An endogenous anti-fibrotic tetrapeptide derived from thymosin beta-4 that curbs collagen deposition and inflammation in preclinical tissue-repair models.
Ac-SDKP is a naturally occurring tetrapeptide cleaved from the N-terminus of thymosin beta-4 by prolyl oligopeptidase and degraded in vivo by angiotensin-converting enzyme (ACE). It is studied for its anti-fibrotic and tissue-reparative signaling, inhibiting collagen synthesis, dampening TGF-beta-1-driven fibroblast activation, and promoting anti-inflammatory macrophage polarization. Preclinical rodent studies of renal, cardiac, pulmonary, and vascular fibrosis show consistent reductions in collagen deposition and inflammatory infiltrate, but no human clinical trials have been completed and it holds no regulatory approval.
Class
Endogenous acetylated tetrapeptide (thymosin beta-4 degradation product)
Routes
Subcutaneous, Intravenous
Category
Healing & Recovery
Researched benefits
What it's studied for
Anti-fibrotic signaling
Ac-SDKP inhibits collagen and fibronectin synthesis and suppresses TGF-beta-1-mediated fibroblast activation. In mouse models of renal fibrosis it consistently reduced collagen deposition and myofibroblast infiltration in both early and late injury stages.
Kidney protection
In a lupus mouse model, Ac-SDKP reduced macrophage and T-cell infiltration, lowered proinflammatory cytokines, blunted complement C5-9 upregulation, and preserved glomerular filtration rate, pointing to renoprotective anti-inflammatory and complement-modulating mechanisms.
Anti-inflammatory macrophage polarization
Across preclinical models Ac-SDKP shifts macrophages toward an anti-inflammatory phenotype and dampens inflammatory infiltrate, contributing to reduced tissue scarring.
Pulmonary fibrosis attenuation
Ac-SDKP inhibited silica-induced pulmonary fibrosis by blocking ALKBH1-mediated m6A demethylation of miR-129-5p, restoring miR-129-5p levels and suppressing inflammatory macrophage activation.
Vascular and endothelial repair
Surface-functionalized Ac-SDKP nanoassemblies on stent coatings accelerated endothelial recovery, reduced neointimal hyperplasia, and limited inflammatory infiltration in animal models, suggesting a role against in-stent restenosis.
Hematopoietic progenitor regulation
Ac-SDKP inhibits hematopoietic stem cell entry into S-phase, a regulatory activity tied to its role in tissue homeostasis downstream of the thymosin beta-4 pathway.
Mechanism
How it works
Ac-SDKP is an endogenous tetrapeptide generated from the N-terminus of thymosin beta-4 by the enzyme prolyl oligopeptidase. Its circulating levels are further regulated by angiotensin-converting enzyme (ACE), which degrades the peptide — a relationship that links ACE inhibition to elevated Ac-SDKP concentrations in vivo.
Its central mechanism is anti-fibrotic. Ac-SDKP inhibits collagen synthesis and fibroblast proliferation and blocks TGF-beta-1-mediated fibroblast activation, the key profibrotic signaling axis. By reducing myofibroblast differentiation and extracellular matrix deposition, it limits scar formation in injured renal, cardiac, pulmonary, and vascular tissue.
Ac-SDKP also acts as an immunomodulator, promoting anti-inflammatory macrophage polarization, reducing macrophage and T-cell infiltration, and lowering proinflammatory cytokine and complement activation. Additional documented activities include promotion of angiogenesis via VEGF upregulation and inhibition of hematopoietic stem cell entry into S-phase, situating it as a homeostatic regulator downstream of the thymosin beta-4 repair pathway.
Evidence
Research & clinical studies (4)
Ac-SDKP Attenuates Silica-Induced Pulmonary Fibrosis by Inhibiting ALKBH1-Mediated m(6)A Demethylation of miR-129-5p
Ac-SDKP inhibited silica-induced pulmonary fibrosis by blocking ALKBH1, restoring miR-129-5p levels and suppressing inflammatory macrophage activation via the Ac-SDKP-ALKBH1-miR-129-5p pathway.
PMID 42172441Device surface-functionalized ac-SDKP nanoassemblies accelerate endothelial recovery through dual anti-inflammatory and endothelial homeostatic mechanisms
Ac-SDKP nanoassemblies on stent coatings promoted endothelial recovery, reduced neointimal hyperplasia, and limited inflammatory infiltration by suppressing macrophage and neutrophil activity while protecting endothelial cells from apoptosis.
PMID 41529529N-Acetyl-Seryl-Aspartyl-Lysyl-Proline: mechanisms of renal protection in mouse model of systemic lupus erythematosus
Ac-SDKP reduced macrophage and T-cell infiltration, decreased proinflammatory cytokines, prevented complement C5-9 upregulation, and preserved glomerular filtration rate in a lupus mouse model.
PMID 25740596Thymosin beta4 and its degradation product, Ac-SDKP, are novel reparative factors in renal fibrosis
Ac-SDKP consistently reduced collagen and fibronectin deposition, decreased myofibroblast and macrophage infiltration, and suppressed profibrotic signaling in both early and late stages of kidney injury.
PMID 23739235Safety
Side effects & considerations
Contraindications & cautions
- Pregnant or nursing
Ac-SDKP is generally considered lower risk in research contexts, but its safety profile in humans is not established given the absence of clinical trials. Individual response varies; review all considerations and consult a qualified professional before use.
FAQ
Ac-SDKP — common questions
What is Ac-SDKP?
Ac-SDKP (N-acetyl-seryl-aspartyl-lysyl-proline) is an endogenous tetrapeptide generated from the N-terminus of thymosin beta-4 by prolyl oligopeptidase and regulated by angiotensin-converting enzyme (ACE). It plays roles in hematopoietic progenitor regulation and anti-fibrotic signaling in renal, cardiac, and vascular tissue.
What is Ac-SDKP primarily studied for?
It is primarily studied for anti-fibrotic activity, cardiac repair, wound healing, and kidney protection in preclinical models.
How does Ac-SDKP work?
It inhibits collagen synthesis and fibroblast proliferation, reduces TGF-beta-1-mediated fibrotic signaling, and promotes anti-inflammatory macrophage polarization, acting as a tissue-homeostasis regulator downstream of the thymosin beta-4 pathway.
Is there human clinical evidence for Ac-SDKP?
No. No human clinical trials have been completed or indexed in PubMed. The available evidence comes from preclinical rodent and in-vitro studies, predominantly of renal, pulmonary, and vascular fibrosis.
What are the side effects of Ac-SDKP?
It is generally considered lower risk in research contexts. Reported contraindications include pregnancy or nursing. Because human data are lacking, its safety profile is not established.
Is Ac-SDKP approved or legal?
Ac-SDKP has no FDA approval and no approved indication in any jurisdiction. It is treated as a research-only compound.
How is Ac-SDKP administered in research?
Reported research routes are subcutaneous and intravenous. There is no validated human dosing protocol.
