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

> A clinical monograph on Ac-SDKP (goralatide/seraspenide), the N-terminal tetrapeptide fragment of thymosin beta-4. Human chemoprotection data (Grade B), preclinical-only anti-fibrosis, and a WADA-prohibited 2026 status.

*Published 2026-06-30 · Updated 2026-07-01 · By Marcus Feld, PharmD, BCPS*

The short answer
Ac-SDKP (goralatide/seraspenide) is the **N-terminal residues 1-4 fragment of thymosin beta-4** and an endogenous anti-fibrotic, anti-inflammatory, pro-angiogenic tetrapeptide. Its **only human evidence is chemoprotection** — small 1990s Phase I-II RCTs that protected blood counts without toxicity (**Grade B**). Every anti-fibrosis claim driving its popularity is **animal/in-vitro only (Grade C)**. It is not FDA-approved and is prohibited in sport.[8](https://peptidevox.com/#r8)[13](https://peptidevox.com/#r13)

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](https://peptidevox.com/#r1)

*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](https://peptidevox.com/#r1) It corresponds to amino acids 1-4 of the 43-residue protein thymosin beta-4 (Tb4).[2](https://peptidevox.com/#r2) 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](https://peptidevox.com/#r3) It is constitutively present in human plasma at roughly 1-5 nM.[10](https://peptidevox.com/#r10)

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](https://peptidevox.com/#r4) 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](https://peptidevox.com/#r6) You can read the registered chemistry record directly at [PubChem CID 65938](https://pubchem.ncbi.nlm.nih.gov/compound/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](https://peptidevox.com/#r5) Second, anti-inflammation: it reduces macrophage infiltration and damps NF-kB and MEK-ERK signaling in injured tissue.[15](https://peptidevox.com/#r15) 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](https://peptidevox.com/#r11)

## 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](https://peptidevox.com/#r8)

  Ac-SDKP evidence by indication

    IndicationBest evidenceGrade

    Chemoprotection / myeloprotection during chemotherapy53-patient double-blind crossover Phase I-II RCT (seraspenide); supportive mouse marrow-protection dataB (human)
    Cardiac fibrosis / post-MI & hypertensive remodelingRat renovascular/aldosterone-salt & post-MI models; antibody-blockade mediator dataC (preclinical)
    Renal fibrosisRodent kidney-injury & diabetic-nephropathy models; additive with ACE inhibitionC (preclinical)
    Pulmonary fibrosisBleomycin mouse model (mortality, collagen, IL-17/TGF-beta/alpha-SMA reduction)C (preclinical)
    Intestinal / hepatic / vascular fibrosis & inflammationExperimental colitis (MEK-ERK) & in-vitro cardiac-fibroblast ER-stress modelsC (preclinical)

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](https://peptidevox.com/#r8) A companion conference report described improved neutrophil recovery in similar regimens.[9](https://peptidevox.com/#r9) 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](https://peptidevox.com/#r10) 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.[11](https://peptidevox.com/#r11)[12](https://peptidevox.com/#r12)

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](https://peptidevox.com/#r5) It reduces tubulointerstitial fibrosis and TGF-beta/DPP-4 signaling in rodent kidney models.[7](https://peptidevox.com/#r7) 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.[13](https://peptidevox.com/#r13)[14](https://peptidevox.com/#r14) It also mitigated experimental colitis via MEK-ERK signaling and attenuated ER-stress-driven collagen production in cardiac fibroblasts in vitro.[15](https://peptidevox.com/#r15)[16](https://peptidevox.com/#r16)

Proven vs hyped
Proven in humans: a myeloprotection signal — protected blood counts without toxicity in a single small 1990s program. Hyped: any claim that Ac-SDKP is a validated human anti-fibrotic or tissue-repair therapy. The preclinical anti-fibrosis data are strong and reproducible across heart, kidney, lung and gut, but there are zero human efficacy trials, and an unresolved pro-angiogenesis/tumor caveat the researchers themselves raise.[13](https://peptidevox.com/#r13)

## 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.[10](https://peptidevox.com/#r10)[13](https://peptidevox.com/#r13) 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](https://peptidevox.com/#r7)

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](https://peptidevox.com/#r8) 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](https://peptidevox.com/#r11) 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](https://peptidevox.com/#r13) A notable pharmacodynamic interaction is that ACE inhibitors substantially raise endogenous levels, which would compound any exogenous dosing.[4](https://peptidevox.com/#r4) 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](https://peptidevox.com/#r8) 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](https://peptidevox.com/#r7) 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](https://peptidevox.com/#r1)

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](https://peptidevox.com/#r2)

**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.

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Source: https://peptidevox.com/peptide-encyclopedia/thymosin-beta-4-frag
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