Anti-scarring peptide: Ac-SDKP (N-acetyl-Ser-Asp-Lys-Pro)
A tiny natural peptide found in the body that reduces scar-tissue buildup in the heart, kidneys, and lungs in animal studies; experimental, not yet an approved drug.
- Class
- Endogenous antifibrotic tetrapeptide / ACE substrate
- Status
- No approved therapeutic use in any jurisdiction
- Best-supported effect
- Reduced collagen deposition and attenuated fibrotic remodeling in rodent organ-fibrosis models (cardiac, renal, pulmonary, hepatic); pharmacodynamic biomarker of ACE-inhibitor activity in humans (observational)
- Main caveat
- All antifibrotic efficacy evidence is preclinical; historical Phase 2 chemoprotection program (goralatide) did not yield approval and does not transfer to antifibrotic dosing; no approved Ac-SDKP product exists anywhere
A researcher, an agent, or an algorithm wrote down the sequence and picked a target to hit.
An AI model like OpenFold3 or AlphaFold built a 3D structure and scored how well it fits the binding site.
A second contributor repeated the computation on their own hardware and the scores matched.
A chemistry service or a researcher ordered the sequence, it was manufactured, and mass spectrometry confirmed the right molecule was produced.
A binding or activity measurement confirmed that it actually does what the computer predicted — or didn't.
Snapshot
Class: Endogenous antifibrotic tetrapeptide / ACE substrate
Evidence tier: Animal-only evidence
Status: No approved therapeutic use in any jurisdiction
Best-supported effect: Reduced collagen deposition and attenuated fibrotic remodeling in rodent organ-fibrosis models (cardiac, renal, pulmonary, hepatic); use as a pharmacodynamic biomarker of ACE-inhibitor activity in humans
Main caveat: All antifibrotic efficacy evidence is preclinical; historical Phase 2 chemoprotection program (goralatide) did not yield approval and does not transfer to antifibrotic dosing; no approved Ac-SDKP product exists anywhere
What this is
Ac-SDKP (N-acetyl-seryl-aspartyl-lysyl-proline) is an endogenous tetrapeptide generated in the body by sequential enzymatic cleavage from the N-terminus of thymosin β4. It is a distinct 4-amino-acid molecule — not a fragment interchangeable with its 43-residue parent. The peptide circulates at low nanomolar concentrations and is degraded almost exclusively by the N-terminal active site of angiotensin-converting enzyme (ACE); this degradation pathway explains why ACE inhibitors raise circulating Ac-SDKP levels several-fold as a pharmacokinetic side effect.
Ac-SDKP has two historical research threads. Through the 1990s, a synthetic form was developed under the name goralatide (Seraspenide) by French researchers (Ipsen/Beaufour) as a chemoprotective agent — the rationale being that reversibly arresting hematopoietic stem-cell cycling during chemotherapy could protect bone marrow from myelotoxicity. That program reached Phase 2 but did not produce an approved product. The contemporary research focus is on Ac-SDKP's antifibrotic activity: preclinical models across cardiac, renal, pulmonary, and hepatic tissue consistently show suppression of fibrotic remodeling. Its most established role in humans today is as a pharmacodynamic biomarker confirming ACE-inhibitor activity, not as a therapeutic.
Evidence map
| Evidence layer | Grade | What it supports |
|---|---|---|
| Human | Anecdotal / biomarker only | Plasma Ac-SDKP rises 4–5 fold in patients on ACE inhibitors; this is a pharmacokinetic observation, not a therapeutic efficacy endpoint. Historical Phase 2 goralatide trials for chemoprotection did not produce approval and are not transferable to antifibrotic dosing. |
| Animal | Moderate to strong | Consistent antifibrotic effects across cardiac (post-MI, angiotensin II-induced hypertension), renal (diabetic nephropathy, unilateral ureteral obstruction), pulmonary (bleomycin-induced), and hepatic (CCl4, bile-duct ligation) fibrosis models in rodents. |
| In vitro | Present (mechanism support) | TGF-β1/Smad2/3 inhibition, Smad7 restoration, EndMT suppression, ERK1/2 attenuation in fibroblasts, macrophage polarization modulation — characterizing the antifibrotic signaling pathway. |
| Computational | None identified | No structure-prediction or docking data attached. |
| Mechanism | Strong (pathway) / Weak (receptor) | TGF-β/Smad inhibition and endothelial-to-mesenchymal transition suppression are well characterized in preclinical systems. A specific high-affinity Ac-SDKP receptor has not been conclusively identified; activity appears to involve pathway modulation rather than a canonical GPCR. |
Claim check
| Claim | Verdict | Evidence layer | Confidence |
|---|---|---|---|
| Reduces fibrosis in cardiac, renal, pulmonary, and hepatic models | Supported (preclinical) | Animal | Medium — consistent across multiple organ models and independent research groups, but all rodent data; human translation unestablished |
| Antifibrotic effect in humans via exogenous administration | Not established | Human | High — no controlled human efficacy trial for antifibrotic use; historical goralatide trials addressed chemoprotection, not fibrosis |
| Useful as a pharmacodynamic biomarker of ACE-inhibitor activity | Supported (human, observational) | Human | High — plasma elevation 4–5 fold on ACE inhibitors is pharmacokinetically characterized in human studies |
| Goralatide was an approved chemoprotective drug | Contradicted | Human | High — goralatide reached Phase 2 but was never approved in any jurisdiction |
| ACE-inhibitor-mediated Ac-SDKP elevation alone explains cardioprotection | Contradicted / not established | Human | Medium — ACE inhibitors also reduce angiotensin II and accumulate bradykinin; the Ac-SDKP contribution is hypothesized and not separately established in controlled human trials |
| Ac-SDKP is interchangeable with thymosin β4 | Contradicted | Animal / in vitro | High — distinct 4-amino-acid peptide with its own catabolic pathway, receptor profile, and signaling — not equivalent to the 43-residue parent |
Experimental exposure
This section reports exposure used in animal experiments and the historical clinical program. It does not establish human dosing for antifibrotic use.
| Context | System | Experimental exposure | Duration | Endpoint | Limitation |
|---|---|---|---|---|---|
| Animal experiment | Rodent cardiac fibrosis models (post-MI, angiotensin II-induced) | Osmotic minipump continuous infusion; specific rates not individually extracted | Weeks-scale rodent study periods | Collagen deposition, cardiac fibrosis markers | Short plasma half-life (minutes) requires continuous infusion; route not practical for human chronic use |
| Animal experiment | Rodent renal fibrosis model (diabetic nephropathy, UUO) | Osmotic minipump infusion; specific rates not individually extracted | Weeks-scale rodent study periods | Renal fibrosis markers, proteinuria | No human renal efficacy data; exposure levels not normalized to human clinical targets |
| Animal experiment | Bleomycin-induced pulmonary fibrosis (rodent) | Osmotic minipump infusion; specific rates not individually extracted | Study-specific duration | Pulmonary fibrosis scoring | Bleomycin model limitations; no human pulmonary efficacy data |
| Clinical trial (historical) | Adults receiving cytotoxic chemotherapy (goralatide Phase 2) | Subcutaneous or intravenous administration; exact regimen not individually extracted | Short chemotherapy-protection course | Hematopoietic protection during chemotherapy | Program discontinued; not transferable to antifibrotic indications or chronic dosing |
Preclinical safety signals
| Signal | System | Notes |
|---|---|---|
| Reversible hematopoietic suppression | Humans (goralatide Phase 2) | Transient bone-marrow effects consistent with the intended chemoprotective mechanism; reported as reversible in historical trials |
| Hematopoietic effects of chronic exogenous exposure | Not characterized | Long-term hematopoietic effects of sustained exogenous Ac-SDKP in non-chemotherapy populations are uncharacterized |
| Pregnancy and lactation safety | Not established | No human safety data; antifibrotic mechanism involves pathways relevant to normal tissue remodeling |
| Combination with ACE inhibitors | Pharmacokinetic concern (not a studied AE) | ACE inhibitors raise endogenous Ac-SDKP 4–5 fold; adding exogenous Ac-SDKP on top creates unstudied combined exposure |
| Effects on malignant cell populations | Not characterized | Historical chemoprotective mechanism involves reversible stem-cell arrest; effects on cancer or myeloproliferative disease are not characterized |
| Research-chemical product safety | Not established | No validated human pharmacokinetic, safety, or purity data for modern research-chemical suppliers |
Regulatory status
| Region / body | Status | Notes |
|---|---|---|
| US (FDA) | Not approved | Not approved for any indication. Not a scheduled substance. No active IND for antifibrotic development. Research-chemical products are sold without human-use claims; this is an unregulated market and not a clinical pathway. |
| EU | Not approved | Per available sources, no EU approval; current status not independently refreshed in this card. |
| UK / Japan / Canada / Australia | Not approved | Per available sources, no approval in these jurisdictions as of 2026. |
| WADA | Not specifically named on Prohibited List | per available sources. Not specifically listed; broader categories relating to hematopoiesis or tissue remodeling may be relevant depending on context. Status not independently refreshed in this card. |
| Clinical trials | No active trials for antifibrotic use | Per available sources, no active registered clinical trials for antifibrotic indications as of 2026. Historical goralatide program completed Phase 2 without approval; not an active program. |
Mechanism
Ac-SDKP is generated from the N-terminus of thymosin β4 by sequential enzymatic action: meprin-α cleaves between residues 4 and 5, and prolyl oligopeptidase completes the release of the tetrapeptide. The resulting peptide circulates at low nanomolar concentrations with a plasma half-life of minutes, limited by near-exclusive degradation at the N-terminal active site of ACE.
The antifibrotic mechanism is multimodal and pathway-mediated rather than receptor-canonical: a specific high-affinity Ac-SDKP receptor has not been conclusively identified. In preclinical systems, Ac-SDKP inhibits TGF-β1 signaling by suppressing phosphorylation of Smad2/3 and restoring Smad7 expression, which is the dominant anti-scarring pathway characterized to date. It also blocks endothelial-to-mesenchymal transition (EndMT) in cardiac and renal endothelium, attenuates ERK1/2 activation in fibroblasts, reduces inflammatory macrophage polarization, and inhibits collagen type I and III deposition across multiple organ models.
In hematopoietic biology — the basis of the historical goralatide program — Ac-SDKP reversibly arrests primitive hematopoietic stem cells in the G1 phase of the cell cycle.
The relationship between Ac-SDKP and ACE is bidirectional: ACE is the dominant degradative enzyme for Ac-SDKP, so ACE inhibitors dramatically elevate circulating Ac-SDKP as a pharmacokinetic consequence. This has led to the hypothesis that part of the well-characterized cardioprotective and antifibrotic benefit of ACE inhibitors is mediated by Ac-SDKP elevation, independently of angiotensin II suppression or bradykinin accumulation — though this has not been separately proven in controlled human trials.
Chemistry
| Field | Value |
|---|---|
| Sequence | Ac-Ser-Asp-Lys-Pro (N-acetyl-seryl-aspartyl-lysyl-proline) |
| Length | 4 amino acids |
| Topology | Linear |
| Modification | N-terminal acetyl group (Ac-) |
| Molecular weight | not individually extracted |
| CAS | not individually extracted |
| Sequence confidence | Verified (source consistent) |
| Origin | Endogenous; cleaved from thymosin β4 N-terminus |
Open questions
- Human antifibrotic efficacy: Whether chronic exogenous Ac-SDKP administration replicates the antifibrotic effects attributed to ACE-inhibitor-mediated endogenous elevation has not been tested in controlled human trials. This is the central unanswered clinical question.
- Receptor identity: A specific high-affinity Ac-SDKP receptor has not been conclusively identified. The multimodal pathway activity suggests either an uncharacterized receptor or non-receptor-mediated signaling; this limits mechanistic target validation.
- Delivery strategy: Oral bioavailability is negligible because of rapid ACE-mediated degradation. No practical delivery strategy for chronic antifibrotic dosing in humans has been developed — osmotic minipump infusion used in preclinical studies is not clinically scalable.
- ACE-inhibitor interaction: Whether adding exogenous Ac-SDKP on top of ACE-inhibitor-elevated endogenous levels produces additive antifibrotic benefit, redundancy, or unanticipated effects has not been studied clinically.
- Long-term hematopoietic effects: Chronic exogenous Ac-SDKP exposure in populations not undergoing chemotherapy may affect hematopoietic stem-cell cycling; no chronic safety data exist.
- Comparative efficacy: Comparative antifibrotic efficacy against approved agents (pirfenidone, nintedanib) in idiopathic pulmonary fibrosis has not been studied.
Research directions for this peptide, selected from the current sources — hypotheses you can explore and model. None of it is proven yet; tap any one to see the full thinking.
Does this peptide actively signal to cells through its own receptor, rather than just being a molecule that the enzyme should not destroy?
If true, discovering that receptor would open a completely new drug target for treating scarring in the heart, lungs, kidneys, and liver, conditions where no approved anti-fibrosis drug currently exists.
If this anti-scarring peptide were delivered through the nose to bypass its rapid breakdown in the blood, could it reduce harmful scarring in the brain after injury?
If true, it could offer a new treatment for traumatic brain injury, reducing the brain scarring that currently limits recovery for millions of accident and combat injury survivors worldwide.
Does removing or changing the acetyl group at the tip of this peptide destroy its anti-scarring effect, proving it is a key part of the active molecule?
If true, it would tell drug designers that any modified version of this peptide must keep the acetyl tip intact, narrowing the design space and preventing wasted effort on analogs that would never work.
Could continuously delivering this anti-scarring peptide during and after chest radiation therapy prevent the lung fibrosis that currently has no approved prevention?
If true, it could protect the roughly one in five chest cancer patients who develop disabling radiation lung fibrosis, improving quality of life after cancer treatment without adding significant toxicity.
Could a version of this peptide that the enzyme cannot digest block the enzyme's specific pocket for this peptide, raising natural levels without affecting blood pressure control?
If true, it could give patients with organ fibrosis the benefits of raised Ac-SDKP without the cough and blood pressure effects of current ACE inhibitors, potentially expanding anti-fibrosis treatment options.
▸full evidence table2 metrics
| metric | value | tool |
|---|---|---|
| ipTM | 0.8792552947998047 | openfold3-mlx |
| ranking score | 0.9313057065010071 | openfold3-mlx |
▸structural qualityopenfold3
| metric | value | note |
|---|---|---|
| gpde | 0.385 | global PDE — lower = better |
| disorder | 0.101 | fraction disordered |
| chain pair ipTM (A, B) | 0.879 | interface quality |
▸3-letter notation
▸recipeopenfold3-mlx 0.3.1
| parameter | value |
|---|---|
| model | openfold3-mlx 0.3.1 |
| weights | — |
| hardware | — |
| mlx version | — |
| python | — |
| random seed | — |
| msa strategy | — |
| diffusion samples | 1 |
| runtime | 79s |
| predicted by | mlx@peptide |
| predicted at | 2026-05-03 |
▸citationbibtex
@peptide{pep10961,
sequence = {SDKP},
target = {ace},
author = {peptidemodel},
year = {2026},
status = {computed}
}