Ac-SDKP (Thymosin Beta-4 Fragment): Evidence, Mechanism & Status

Ac-SDKP (N-acetyl-Ser-Asp-Lys-Pro; also goralatide or seraspenide) is an endogenous tetrapeptide carved from the N-terminus of thymosin beta-4, marketed in peptide-community circles as an anti-fibrotic and tissue-repair agent. It has a genuinely interesting biology and a real, if dated, human signal — but the evidence map is lopsided, and it is frequently confused with TB-500. This monograph separates what is proven from what is hyped.1

This article is informational and editorial content for research and educational purposes only. It is not medical advice, not a protocol to follow, and not a sourcing guide. Ac-SDKP is not an FDA-approved drug; it is sold as a research chemical not for human use and is prohibited in sport. Dosing figures are reported strictly as seen in the published literature for completeness — not as recommendations. Consult a licensed clinician before any health decision.

What is Ac-SDKP and how does it work?

Ac-SDKP is the N-acetylated tetrapeptide N-acetyl-Seryl-Aspartyl-Lysyl-Prolyl (molecular formula C20H33N5O9, MW about 487.5 Da, PubChem CID 65938, CAS 120081-14-3 for the acetyl form).1 It corresponds to amino acids 1-4 of the 43-residue protein thymosin beta-4 (Tb4).2 Endogenously it is generated by a two-step cleavage of Tb4: because prolyl-oligopeptidase can only hydrolyze short substrates, an upstream metalloprotease, meprin-alpha, first releases shorter N-terminal intermediates, after which prolyl-oligopeptidase liberates the Ac-SDKP tetrapeptide.3 It is constitutively present in human plasma at roughly 1-5 nM.10

The defining pharmacology is its degradation. Ac-SDKP is the preferred natural substrate of the N-terminal catalytic domain of angiotensin-converting enzyme (ACE), which hydrolyzes it to inactive fragments and gives it a plasma half-life of only about 4-5 minutes after IV dosing.4 Consequently, ACE inhibitors block its breakdown and raise its plasma concentration up to about fivefold in humans — a discovery that reframed part of the anti-fibrotic benefit of ACE inhibitors such as captopril as being mediated by accumulated endogenous Ac-SDKP.6 You can read the registered chemistry record directly at PubChem CID 65938.

Mechanistically Ac-SDKP works through three converging arms. First, anti-fibrosis: it suppresses the TGF-beta/Smad2-3 and CTGF axis, blocking fibroblast-to-myofibroblast (alpha-SMA) differentiation and collagen synthesis, and antibody-neutralization experiments confirm it is a required mediator of captopril's anti-fibrotic effect on the heart.5 Second, anti-inflammation: it reduces macrophage infiltration and damps NF-kB and MEK-ERK signaling in injured tissue.15 Third, it is pro-angiogenic while simultaneously acting as a negative regulator of hematopoietic stem-cell entry into S-phase, keeping pluripotent stem cells quiescent.11

What is the evidence by indication?

The critical separation: Ac-SDKP has human RCT evidence only for chemoprotection (Grade B). Every anti-fibrotic and tissue-repair claim is supported only by animal and in-vitro data (Grade C), with no human efficacy trials. Do not read the preclinical anti-fibrotic literature as a human claim.8

Chemoprotection is the only indication studied in humans. In the Phase I-II crossover trial, 53 cancer patients on cytarabine and ifosfamide monochemotherapy received seraspenide, which produced significant protection of peripheral blood cells and was devoid of toxicity.8 A companion conference report described improved neutrophil recovery in similar regimens.9 Human pharmacokinetics in healthy volunteers and chemo patients confirmed a stable low-nanomolar endogenous baseline and rapid clearance of exogenous peptide — establishing the short-half-life challenge that limited development.10 Preclinically, goralatide protected bone-marrow stem and progenitor cells from cytarabine, cyclophosphamide and carboplatin by holding them out of cycle, and protected against doxorubicin toxicity, improving murine survival.1112

The anti-fibrotic literature is robust but entirely preclinical. In rat models, Ac-SDKP prevents and reverses left-ventricular collagen deposition and TGF-beta/CTGF signaling independent of blood-pressure change, and antibody-blockade of Ac-SDKP abolishes much of captopril's anti-fibrotic effect.5 It reduces tubulointerstitial fibrosis and TGF-beta/DPP-4 signaling in rodent kidney models.7 In the bleomycin mouse lung model (0.6 mg/kg IP biweekly), given preventively or therapeutically, it reduced 21-day mortality, lung edema, soluble collagen and fibrosis score, and near-completely blocked bleomycin-induced IL-17, TGF-beta and alpha-SMA upregulation — though the authors explicitly caution about a possible role in malignancy before any clinical use.1314 It also mitigated experimental colitis via MEK-ERK signaling and attenuated ER-stress-driven collagen production in cardiac fibroblasts in vitro.1516

What doses appear in the literature, and is it safe?

Reported strictly as information, not a protocol. Ac-SDKP is parenteral only — a peptide that is not orally bioavailable — and its roughly 4-5-minute ACE-driven half-life means a single bolus is cleared almost immediately. Human chemoprotection used continuous IV infusion, while animal anti-fibrosis studies used osmotic minipump or repeated intraperitoneal injection at roughly 0.6-0.8 mg/kg/day, for example 0.6 mg/kg IP biweekly in the bleomycin lung model.1013 Because ACE inhibitors raise endogenous Ac-SDKP roughly fivefold, much translational interest is in leveraging ACE inhibition or building ACE-resistant analogs rather than infusing the native peptide.7

On safety, the short-term human signal is benign: in the Phase I-II trial seraspenide was devoid of toxicity, and as an endogenous low-nanomolar peptide acute tolerability appears favorable — but the human exposure base is tiny and short-term.8 The defining on-target action, suppressing hematopoietic stem-cell cycling, is therapeutically useful as chemoprotection but a theoretical liability (blunted marrow response) outside that context.11 The dominant theoretical concern is mechanistic: like its parent Tb4, Ac-SDKP is pro-angiogenic, and the lung-fibrosis authors explicitly flag a potential role in malignancy that must be resolved before clinical use.13 A notable pharmacodynamic interaction is that ACE inhibitors substantially raise endogenous levels, which would compound any exogenous dosing.4 Bottom line: short-term data look benign but are minimal, long-term safety is unestablished, and the angiogenesis/tumor question is unresolved.

What is the FDA and WADA status in 2026?

Ac-SDKP/goralatide has no FDA-approved drug product and no active application for any indication; its 1990s chemoprotection development (seraspenide, Ipsen/Beaufour) did not reach approval.8 The broader thymosin-beta-4 family, including the TB-500 fragment, was placed on the FDA 503A Category 2 bulk-drug-substance list as a significant safety risk and not eligible for routine compounding, with an advisory-committee review of peptide bulk substances slated for July 2026.7 Ac-SDKP itself is neither approved nor compoundable and is sold only as an unapproved research chemical, not for human use, with no guarantee of identity or purity.1

For athletes the picture is unambiguous. The WADA 2026 Prohibited List bans thymosin-beta-4 and its derivatives at all times under category S2 (Peptide Hormones, Growth Factors, Related Substances and Mimetics). As an endogenous N-terminal cleavage product of thymosin beta-4, Ac-SDKP sits within that prohibited family, and the explicitly named member is TB-500. Any tested athlete should treat it as prohibited in and out of competition, and should consult the current year's list because it is updated annually.2

Bottom line. Ac-SDKP is one of the more mechanistically credible repair peptides — a true endogenous tetrapeptide and the molecular link explaining part of why ACE inhibitors are anti-fibrotic — but its evidence map is lopsided. The only thing tested in humans is its chemoprotective effect (Grade B); every anti-fibrosis use that drives its popularity is animal/in-vitro only (Grade C), with an unresolved tumor caveat. It is not FDA-approved, sits in the WADA-prohibited thymosin-beta-4 family, and is not the same molecule as TB-500. Regulatory facts here are current as of June 2026 and should be re-verified against the latest FDA compounding actions and the annually updated WADA list.