Ac-SDKP

Healing & Recovery

Also known as: N-Acetyl-Seryl-Aspartyl-Lysyl-Proline, Goralatide, Seraspenide, AcSDKP, Thymosin Beta-4 Fragment

Anti-Fibrotic PeptidesResearch phase: Extensive preclinical, limited clinical dataRegulatory: Not approved by any regulatory agency. Research peptide. Endogenous peptide — produced naturally in the body from TB-4 metabolism. ACE inhibitor mechanism of fibrosis protection partly attributed to Ac-SDKP elevation.

Mechanism

Ac-SDKP is a small four-amino-acid peptide that your body naturally produces when thymosin beta-4 (TB-500) is broken down by prolyl oligopeptidase. It is one of the most potent natural anti-fibrotic (anti-scarring) agents known. It prevents fibrosis in the heart, kidneys, liver, and lungs by blocking the transformation of normal cells into scar-producing myofibroblasts. Interestingly, ACE inhibitors (common blood pressure drugs) raise Ac-SDKP levels because ACE is the enzyme that normally breaks it down — this may partly explain why ACE inhibitors protect against organ fibrosis.

Technical detail

Ac-SDKP (N-acetyl-seryl-aspartyl-lysyl-proline) is a tetrapeptide released from thymosin β4 by prolyl oligopeptidase (POP). It is degraded by angiotensin-converting enzyme (ACE) — hence ACE inhibitors increase circulating Ac-SDKP 5-fold. Anti-fibrotic mechanism: (1) Inhibits TGF-β/Smad2/3 signaling, the master pathway driving fibroblast-to-myofibroblast transition (FMT); (2) Blocks connective tissue growth factor (CTGF) expression; (3) Reduces collagen I and III deposition in fibrotic tissues; (4) Inhibits inflammatory macrophage infiltration and M2 macrophage-driven fibrosis; (5) Suppresses endothelial-to-mesenchymal transition (EndMT). Also regulates hematopoietic stem cell quiescence — maintains HSCs in G0 phase, protecting them from cell-cycle-specific damage (originally called goralatide for this function). Anti-fibrotic effects demonstrated in animal models of cardiac fibrosis (MI, hypertension), renal fibrosis (UUO, diabetic nephropathy), hepatic fibrosis (CCl4, BDL), and pulmonary fibrosis (bleomycin).

Evidence

  • [Meta-analysis of Ac-SDKP inhibition of Pulmonary fibrosis in animal models].

    H B Gong et al. (2023) — Zhonghua Lao Dong Wei Sheng Zhi Ye Bing Za Zhi — PMID: 37248179

    Chinese/English PubMed-indexed meta-analysis of 18 animal studies (428 models) found Ac-SDKP significantly reduced alpha-SMA, type I/III collagen, TGF-beta, and nodule area in pulmonary fibrosis models, supporting antifibrotic preclinical activity.

    moderate

  • A Small Peptide Ac-SDKP Inhibits Radiation-Induced Cardiomyopathy

    (2018) — Ovid Technologies (Wolters Kluwer Health) — PMID: 10.1161/circheartfailure.117.004867

    The study found that Ac-SDKP inhibits radiation-induced cardiomyopathy in a rat model by reducing inflammation, fibrosis, and macrophage activation. It shows therapeutic potential for counteracting radiation-induced cardiotoxicity.

    emerging

  • Thymosin β4 and its degradation product, Ac-SDKP, are novel reparative factors in renal fibrosis.

    Zuo Y et al. (2013) — Kidney Int — PMID: 23739235

    In unilateral ureteral obstruction models, Ac-SDKP reduced collagen/fibronectin deposition, myofibroblasts, macrophages, and profibrotic signaling in both wild-type and PAI-1 knockout mice, supporting consistent antifibrotic activity in kidney injury.

    moderate

  • Ac-SDKP ameliorates the progression of lupus nephritis in MRL/lpr mice

    (2012) — Elsevier BV — PMID: 10.1016/j.intimp.2012.07.023

    Ac-SDKP treatment reduced proteinuria, improved renal function, decreased inflammatory infiltrates, and inhibited renal fibrosis in MRL/lpr mice.

    emerging

  • Decreased Endogenous Levels of Ac-SDKP Promote Organ Fibrosis

    (2007) — Ovid Technologies (Wolters Kluwer Health) — PMID: 10.1161/hypertensionaha.106.084103

    The study found that decreased endogenous levels of Ac-SDKP in rats led to increased cardiac and renal fibrosis, and accelerated interstitial cardiac fibrosis when combined with angiotensin II. This suggests Ac-SDKP plays a physiological role in preventing organ collagen accumulation.

    moderate

  • Prolyl Oligopeptidase Is Involved in Release of the Antifibrotic Peptide Ac-SDKP

    (2004) — Ovid Technologies (Wolters Kluwer Health) — PMID: 10.1161/01.hyp.0000126172.01673.84

    The study found that prolyl oligopeptidase (POP) is involved in the release of the antifibrotic peptide Ac-SDKP from thymosin-β4. POP inhibitors decreased Ac-SDKP generation in kidney cortex homogenates, and long-term administration of a POP inhibitor decreased endogenous levels of Ac-SDKP in rats.

    emerging

  • Ac-SDKP Reverses Cardiac Fibrosis in Rats With Renovascular Hypertension

    (2003) — Ovid Technologies (Wolters Kluwer Health) — PMID: 10.1161/01.hyp.0000100423.24330.96

    Ac-SDKP was found to reverse cardiac fibrosis in rats with renovascular hypertension in a dose-dependent manner, by decreasing TGF-β and CTGF. The study used doses of 400 or 800 μg/kg per day SC for 8 weeks.

    emerging
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