Ac-SDKP
An endogenous tetrapeptide cleaved from thymosin β4 with broad antifibrotic activity across the heart, kidney, lung, and liver — historically developed as the chemoprotective drug goralatide and more recently studied as a biomarker of ACE-inhibitor activity.
What is Ac-SDKP?
Ac-SDKP (N-acetyl-seryl-aspartyl-lysyl-proline) is an endogenous tetrapeptide produced in the body by enzymatic cleavage from the N-terminus of thymosin β4. It circulates at low nanomolar concentrations in plasma and is degraded almost exclusively by the N-terminal active site of angiotensin-converting enzyme (ACE) — which is why ACE inhibitors raise circulating Ac-SDKP several-fold. In the 1990s, a synthetic form was developed under the name goralatide (Seraspenide) as a chemoprotective agent — meant to reversibly arrest hematopoietic stem-cell proliferation during chemotherapy to spare bone marrow. That development program did not yield an approved product. More recent research has shifted focus to Ac-SDKP's broad antifibrotic activity across cardiac, renal, pulmonary, and hepatic tissue, and to its role as a pharmacodynamic biomarker of ACE activity.
What Ac-SDKP Is Investigated For
Ac-SDKP is primarily a research molecule with two historical through-lines. The first is its 1990s development as goralatide, a chemoprotective agent meant to reversibly quiesce hematopoietic stem cells during cytotoxic chemotherapy — an idea that made it into Phase 2 but never produced an approved product. The second, and the focus of current research, is its antifibrotic activity. Preclinical models across cardiac, renal, pulmonary, and hepatic tissue consistently show that Ac-SDKP reduces collagen deposition, inhibits TGF-β/Smad signaling, suppresses endothelial-to-mesenchymal transition, and attenuates inflammation-driven fibrotic remodeling. The clearest clinical footprint today is as a biomarker: circulating Ac-SDKP rises several-fold in patients on ACE inhibitors (because ACE is its dominant catabolic enzyme), and it is used pharmacologically to verify ACEi activity. There is no approved Ac-SDKP therapeutic, no established clinical dose for antifibrotic indications, and no human safety database beyond the historical goralatide trials. Products sold online as "Ac-SDKP" are research chemicals without validated human pharmacology.
History & Discovery
Ac-SDKP was first described in the 1980s in bone marrow research as an endogenous inhibitor of hematopoietic stem-cell proliferation. It was developed through the 1990s as goralatide (Seraspenide) by French researchers (Ipsen/Beaufour) for chemoprotection — the idea that reversibly arresting marrow cycling during chemotherapy could reduce myelotoxicity. Phase 2 trials were conducted but the program did not yield approval. A parallel research line characterized Ac-SDKP as an ACE substrate, and by the early 2000s the antifibrotic activity across cardiac, renal, pulmonary, and hepatic tissue had been described in detail, largely through work from Oscar Carretero's group at Henry Ford Hospital and collaborators. The modern research footprint is dominated by this antifibrotic and ACE-biomarker literature rather than the original hematopoietic framing.
How It Works
Your body cleaves a small four-amino-acid peptide — Ac-SDKP — from a larger regenerative protein called thymosin β4. In animal studies, Ac-SDKP reduces scarring (fibrosis) in the heart, kidneys, lungs, and liver by dampening the signals that tell tissue to lay down collagen. In people, the main reason Ac-SDKP matters clinically today is that ACE inhibitors like lisinopril raise its levels several-fold, and part of the long-term protective effect of ACE inhibitors may come from that elevation. No Ac-SDKP drug is approved.
Ac-SDKP is generated from thymosin β4 by sequential action of meprin-α (cleaving between residues 4 and 5) and prolyl oligopeptidase. It circulates at low nanomolar concentrations and is degraded almost exclusively by the N-terminal active site of angiotensin-converting enzyme (ACE), giving it a short plasma half-life of minutes. Pharmacologically, Ac-SDKP's antifibrotic mechanism is multimodal: it inhibits TGF-β1 signaling by suppressing phosphorylation of Smad2/3 and restoring Smad7 expression, blocks endothelial-to-mesenchymal transition (EndMT) in cardiac and renal endothelium, reduces inflammatory macrophage polarization, attenuates ERK1/2 activation in fibroblasts, and inhibits collagen type I and III deposition in multiple organ models. In hematopoietic biology, Ac-SDKP reversibly arrests cycling of primitive hematopoietic stem cells in the G1 phase, which was the basis for its 1990s development as a chemoprotective agent (goralatide). The relationship to ACE is bidirectional: ACE degrades Ac-SDKP, so ACE inhibitors elevate plasma Ac-SDKP, and elevated Ac-SDKP is considered a contributor to the antifibrotic effects of ACE inhibitors that are not explained by angiotensin II reduction or bradykinin accumulation alone.
Evidence Snapshot
Human Clinical Evidence
Limited. Historical Phase 2 goralatide trials for chemoprotection did not produce an approved product and are not directly applicable to antifibrotic dosing. Current clinical data are limited to biomarker studies showing 4–5 fold elevation of plasma Ac-SDKP in patients on ACE inhibitors.
Animal / Preclinical
Moderate to strong across organ-fibrosis models. Consistent antifibrotic effects in cardiac (post-MI, angiotensin II-induced), renal (diabetic nephropathy, unilateral ureteral obstruction), pulmonary (bleomycin-induced), and hepatic (CCl4, bile-duct ligation) fibrosis models.
Mechanistic Rationale
Strong for TGF-β/Smad inhibition and EndMT suppression. Strong pharmacokinetic characterization of its degradation by ACE. Weaker for receptor identity — a specific high-affinity Ac-SDKP receptor has not been conclusively established, and much of its signaling appears to act via modulation of other pathways rather than a canonical GPCR.
Research Gaps & Open Questions
What the current literature has not yet settled about Ac-SDKP:
- 01No specific high-affinity Ac-SDKP receptor has been conclusively identified — much of its activity is inferred from pathway modulation rather than canonical GPCR pharmacology.
- 02Whether chronic exogenous Ac-SDKP dosing replicates the antifibrotic effects attributed to ACE-inhibitor-mediated endogenous elevation has not been directly tested in humans.
- 03Long-term hematopoietic effects of sustained exogenous Ac-SDKP exposure in patients not undergoing chemotherapy are uncharacterized.
- 04Comparative efficacy against approved antifibrotics (pirfenidone, nintedanib) in idiopathic pulmonary fibrosis has not been studied.
- 05Oral bioavailability is negligible and no practical delivery strategy for chronic antifibrotic dosing in humans has been developed.
Forms & Administration
Ac-SDKP is not available as an approved therapy. In preclinical antifibrotic studies, it is most commonly delivered by osmotic minipump infusion because of its short plasma half-life (minutes, owing to rapid ACE-mediated degradation). Historical goralatide clinical trials used subcutaneous or intravenous administration. The practical clinical path to elevating endogenous Ac-SDKP today is through ACE inhibitor therapy, which raises plasma levels 4–5 fold as a pharmacologic side effect.
Common Questions
Who Ac-SDKP Is NOT For
- •Pregnancy and lactation — no human safety data, and the antifibrotic mechanism involves pathways important in normal tissue remodeling.
- •Active cancer or myeloproliferative disease — the historical chemoprotective mechanism involves reversible arrest of stem-cell cycling, and effects on malignant cell populations are not characterized.
- •Unmonitored concurrent use of ACE inhibitors — ACE inhibition dramatically elevates endogenous Ac-SDKP, so adding exogenous Ac-SDKP on top compounds exposure in ways not studied clinically.
- •Any clinical use outside a registered research protocol — there is no approved product and no validated dose.
Drug & Supplement Interactions
The most characterized interaction is with ACE inhibitors (lisinopril, ramipril, captopril, enalapril, etc.), which raise plasma Ac-SDKP 4–5 fold by blocking its primary catabolic pathway. This is a pharmacokinetic fact rather than a known adverse interaction, but any clinical dosing of exogenous Ac-SDKP would need to account for it. ARBs (angiotensin receptor blockers) do not significantly affect Ac-SDKP clearance. Theoretical interactions with other antifibrotic or cytotoxic therapies exist but are uncharacterized, and Ac-SDKP's effect on monocyte/macrophage polarization raises theoretical considerations around combination with immunomodulators, though none of this has been studied clinically.
Safety Profile
Common Side Effects
Cautions
- • Not FDA-approved for any indication
- • No active clinical development program for antifibrotic use
- • Research-chemical products are unvalidated — no human pharmacokinetic, safety, or purity data for modern suppliers
- • Historical Phase 2 goralatide data are limited in scope and are not transferable to chronic antifibrotic dosing
What We Don't Know
What dose and route produce sustained plasma Ac-SDKP elevation mimicking the antifibrotic concentrations seen in preclinical models, whether chronic exogenous administration replicates the antifibrotic effects attributed to ACE-inhibitor-mediated endogenous elevation, and whether long-term hematopoietic or immunologic effects emerge with chronic exposure.
Legal Status
United States
Not FDA-approved for any indication. Not a scheduled substance. No active IND for antifibrotic development. Research-chemical suppliers offer Ac-SDKP without human-use claims; this is an unregulated grey market and not a clinical pathway.
International
Not approved in the EU, UK, Japan, Australia, or Canada. No active registered clinical trials for antifibrotic indications as of 2026.
Sports & Competition
Not specifically named on the WADA Prohibited List, but athletes should be aware that peptides acting on tissue remodeling and hematopoiesis may fall under broader WADA categories depending on context. A TUE would not apply for a non-approved compound.
Regulatory status changes over time. Verify current local rules with a qualified professional.
Myths & Misconceptions
Myth
Ac-SDKP is a form of thymosin β4.
Reality
Ac-SDKP is cleaved from thymosin β4 but is a distinct 4-amino-acid peptide with its own pharmacology, degradation pathway (ACE), and signaling profile. The parent molecule is 43 amino acids and has broader regenerative effects — the two overlap but are not interchangeable.
Myth
Goralatide was FDA-approved in the 1990s.
Reality
Goralatide reached Phase 2 for chemoprotection but was never approved. No Ac-SDKP product has ever been approved in any jurisdiction.
Myth
Taking ACE inhibitors gives you the full Ac-SDKP antifibrotic effect.
Reality
ACE inhibitors do raise endogenous Ac-SDKP 4–5 fold, and this likely contributes to their cardioprotective effects. But the plasma elevation achieved is modest compared to the levels used in preclinical antifibrotic infusion studies, and the antifibrotic benefits of ACE inhibitors also come from angiotensin II reduction and bradykinin accumulation — not from Ac-SDKP alone.
Published Research
7 studiesAc-SDKP: An Endogenous Regulator of Tissue Repair and Fibrosis
Ac-SDKP Attenuates Bleomycin-Induced Pulmonary Fibrosis in Rats
N-acetyl-seryl-aspartyl-lysyl-proline Prevents Renal Insufficiency and Fibrosis in a Model of Progressive Diabetic Nephropathy
Ac-SDKP Reverses Cardiac Fibrosis in Rats with Renovascular Hypertension
ACE Inhibitors Increase Plasma Ac-SDKP Levels in Humans
Goralatide (Seraspenide) in Chemotherapy-Induced Myelosuppression: A Phase II Trial
N-Acetyl-Seryl-Aspartyl-Lysyl-Proline: A Valuable Endogenous Anti-Fibrotic Peptide
Quick Facts
- Class
- Endogenous Antifibrotic Peptide
- Evidence
- Preliminary
- Safety
- Limited Data
- Updated
- Apr 2026
- Citations
- 7PubMed
Also known as
Tags
Evidence Score
Clinical Trials
View Clinical TrialsLinks to ClinicalTrials.gov for reference. Listing does not imply endorsement.