Deep research
About TB-500 Fragment (Ac-SDKP)
Ac-SDKP (N-acetyl-seryl-aspartyl-lysyl-proline) is a naturally occurring tetrapeptide with a molecular weight of approximately 487 Da and the molecular formula C20H33N5O9. It is the N-terminal fragment of Thymosin Beta-4, released in vivo by the enzyme prolyl oligopeptidase (POP), which cleaves Tbeta4 between the Pro4 and Asp5 residues. Ac-SDKP circulates in human plasma at concentrations of 1-5 nM under normal physiological conditions and is degraded almost exclusively by angiotensin-converting enzyme (ACE). This explains why ACE inhibitor drugs (captopril, enalapril, lisinopril, ramipril) consistently raise plasma Ac-SDKP levels by 4-5x, and some researchers have proposed that the cardioprotective benefits of ACE inhibitors may be partially mediated through Ac-SDKP accumulation.
The primary mechanism of action of Ac-SDKP is anti-fibrotic. It directly inhibits the proliferation of fibroblasts and their differentiation into myofibroblasts, the activated cell type responsible for excessive collagen deposition and scar formation in damaged tissues. At the molecular level, Ac-SDKP blocks the TGF-beta/Smad2/3 signaling pathway, which is the central driver of fibrosis across all organ systems. It specifically reduces phosphorylation of Smad2 and Smad3 while increasing expression of the inhibitory Smad7, effectively shutting down the pro-fibrotic signaling cascade. This mechanism has been demonstrated in cardiac, renal, hepatic, and pulmonary fibroblast models.
The research evidence for Ac-SDKP spans multiple organ systems. In a study published in Peptides (Peng et al., 2014), Ac-SDKP reduced cardiac fibrosis by approximately 45% in hypertensive rat models as measured by hydroxyproline content and Masson's trichrome staining. Rasoul et al. (Life Sciences, 2004) demonstrated that Ac-SDKP reduced renal interstitial fibrosis by 40% in aldosterone-salt hypertensive rats. In pulmonary fibrosis models (Conte et al., FASEB Journal, 2003), Ac-SDKP inhibited lung collagen deposition and reduced fibroblast proliferation by 60%. Ac-SDKP also promotes angiogenesis: Liu et al. (Angiogenesis, 2003) showed it stimulates endothelial cell proliferation, migration, and tube formation in vitro, and promotes neovascularization in ischemic tissues in vivo.
Pharmacokinetically, Ac-SDKP has a short plasma half-life of approximately 4-5 minutes under normal conditions, due to rapid hydrolysis by ACE. In the presence of ACE inhibitors, the half-life extends significantly, and plasma concentrations rise 4-5x. Despite its short half-life, tissue-level effects persist because Ac-SDKP accumulates intracellularly in target tissues (particularly fibroblasts and endothelial cells) and its anti-fibrotic signaling effects (Smad pathway modulation) continue after the peptide itself is cleared. As a tetrapeptide of only 487 Da, Ac-SDKP has excellent tissue penetration, crossing capillary barriers and reaching interstitial compartments far more efficiently than full-length TB-500 (4921 Da). Subcutaneous bioavailability is high, and the peptide distributes rapidly to cardiac, renal, hepatic, and pulmonary tissues.
Ac-SDKP lyophilized powder should be stored at -20C, where it is stable for 24+ months. Reconstitute with bacteriostatic water or sterile saline. The reconstituted solution should be stored at 2-8C and used within 28 days. Due to its small size, Ac-SDKP is more resistant to aggregation and freeze-thaw degradation than larger peptides. The lyophilized powder is hygroscopic and should be protected from moisture. The reconstituted solution should be clear and colorless.
Published research protocols have administered Ac-SDKP via subcutaneous injection or osmotic minipump at doses of 400-800 mcg/kg/day in rodent models, typically for 2-8 week periods. The minipump delivery method is common in research settings to overcome the short half-life and ensure sustained tissue exposure. Subcutaneous injection protocols typically use 2-3 daily administrations to maintain tissue concentrations. Anti-fibrotic effects are typically measurable by histological assessment within 2-4 weeks of treatment initiation.
The safety profile of Ac-SDKP is favorable. As an endogenous peptide present in normal human plasma, it has a well-characterized physiological role. In animal studies, Ac-SDKP administration at doses up to 1600 mcg/kg/day for 8 weeks produced no adverse effects on blood pressure, heart rate, renal function, or hematological parameters. It does not promote tumor growth in published studies; in fact, its original characterization in the 1980s was as a hematopoietic stem cell inhibitor (it reversibly inhibits entry of hematopoietic stem cells into S-phase), a property that has been explored for bone marrow protection during chemotherapy.
