Ac-SDKP (N-acetyl-seryl-aspartyl-lysyl-proline) is a very small protein fragment derived from another natural protein called thymosin beta 4. In the body, specific enzymes break down thymosin beta 4 into smaller pieces, and one of the results of this process is Ac-SDKP [1]. This small molecule is important because it helps protect organs from scarring (fibrosis), which happens when too much rigid tissue builds up after injury or disease. The problem is that Ac-SDKP doesn't stay around for long in the body—it's quickly broken down by an enzyme called ACE (angiotensin-converting enzyme). Interestingly, ACE-blocking drugs (like some blood pressure medications) can increase Ac-SDKP levels up to fivefold, enhancing its protective effects [1].
Initially, scientists thought that Ac-SDKP's main role was to keep blood stem cells from growing too fast. However, more recent studies show that its larger role is in tissue healing and protection. It helps stop the excessive growth of scar tissue in organs such as the heart, lungs, liver and kidneys. For example, it reduces the activity of certain signals that cause cells to produce too much collagen (the main protein of scar tissue) and prevents repair cells (fibroblasts) from turning into scar-forming cells. For kidney disease, Ac-SDKP shows real promise. Not only does it help the kidneys function better, but it also reduces scarring by blocking the access of too many immune cells and alleviating the harmful processes that usually worsen damage. In short, Ac-SDKP acts as a natural „anti-scarring” and „tissue-protecting” molecule in the body. It promotes healing, reduces inflammation and may be useful in treating diseases in which scarring and tissue damage play an important role.
Ac-SDKP protects the heart (based on animal studies)
W kilku badaniach naukowych opisano potencjał Ac-SDKP w zakresie zdrowia serca zarówno w nagłych przypadkach, jak i w przypadku długotrwałych problemów. W modelu mysiego zawału serca Nakagawa i wsp. podawali Ac-SDKP w dawce 1,6 mg/kg/dobę za pomocą niewielkiej pompy podskórnej i stwierdzili wyraźne korzyści: rozdarcia ściany serca (pęknięcia serca) spadły z 51,0% do 27,3%, a śmiertelność spadła z 56,9% do 31,8%. Peptyd wydawał się działać poprzez uspokajanie komórek odpornościowych„pierwszej pomocy”, które mogą pogłębiać uszkodzenia (makrofagi M1), nie zmieniając jednocześnie pomocnych makrofagów naprawczych (M2) ani neutrofili. Spowolnił również działanie enzymu (MMP-9), który rozkłada tkankę serca po zawale, podczas gdy inny marker (MPO) nie uległ zmianie, co sugeruje ukierunkowane, celowe działanie [2].
In the case of cardiac scarring caused by long-term high blood pressure, Peng et al. showed that Ac-SDKP can reduce existing scar tissue, not just prevent it. In rats with a well-established model of hypertension, daily administration of Ac-SDKP at a dose of 400-800 µg/kg (subcutaneously) for 8 weeks reduced the amount of collagen in the heart - the main sign of scarring - in a dose-dependent manner (the higher dose was more effective). Blood pressure per se did not fall, and normal responses to angiotensin I and bradykinin were unaffected, so the benefit was not solely due to lowering blood pressure. Ac-SDKP blood levels increased 2-5-fold, and key „scar-inducing” signals in the heart (TGF-β and CTGF) were reduced, confirming a direct anti-scarring effect [3]. After myocardial infarction, persistent edema and scarring can lead to heart failure. Yang et al. tested Ac-SDKP both early (to prevent damage) and later (to reverse damage). In both cases, total cardiac collagen content decreased (for example, from ~24 to ~15 µg/mg in the prevention group and from ~23 to ~14 µg/mg in the reversal group). Harmful accumulation of immune cells also decreased: macrophages decreased by about a third in each group, and TGF-β-positive cells decreased in parallel. These benefits were achieved without lowering blood pressure or reducing the size of the heart, and pumping power was not markedly improved in the prophylactic group. Nevertheless, the steady decrease in scarring and inflammation indicates an improvement in cardiac structure over time [4].
Ac-SDKP may also explain some of the „additional” tissue benefits observed with ACE-inhibiting drugs. Rasoul et al. compared a model of angiotensin II-induced hypertension with groups receiving captopril or Ac-SDKP (400-800 µg/kg/day). This raised blood levels several-fold and reproduced many of the protective properties similar to ACE inhibitors: less cellular hypertrophy in the heart, fewer macrophages and mast cells, lower levels of TGF-β and CTGF, and less collagen accumulation. Importantly, these benefits occurred without lowering blood pressure or reducing cardiac thickening, indicating an indirect protective effect on cardiac tissue [5]. Ac-SDKP slows scar formation in the heart at the cellular level. In cultured rat cardiac support cells (fibroblasts) in the laboratory, Rhaleb et al. tested very low doses of Ac-SDKP (0.05-100 nmol/l) and found two key effects: a reduction in cell growth (DNA copying) to normal at around 1 nmol/l, and a reduction in collagen (the main „scar” protein) produced in response to endothelin-1, a potent scarring signal. Lower doses worked best on collagen; very high doses were less effective. The peptide appeared to silence a common switch in cellular signals (p44/42 MAPK/ERK), and a known MAPK blocker provided the same benefit. Put simply, Ac-SDKP commands fibroblasts to slow down both proliferation and excessive scar formation, presumably by reducing the activity of a key growth pathway [6].
Furthermore, it protects the heart from damage caused by galectin-3. In studies on adult rats, Liu et al. administered galectin-3 (a protein that causes inflammation and scarring) for four weeks and observed an increased number of inflammatory cells, thicker heart walls, more pronounced scarring around blood vessels and between cells, higher levels of TGF-β/Smad3 signaling (a pro-scarring pathway), and reduced pumping function on echocardiography. The addition of Ac-SDKP (800 µg/kg/day) prevented most of these changes: it reduced the number of inflammatory cells, scarring, and thickening of the heart walls, and improved heart function. The data suggest that it protects the heart by switching off the TGF-β/Smad3 „scarring switch” and mitigating inflammation [7].
Furthermore, it reduces cardiac scarring in the context of sustained hypertension without altering blood pressure itself. Using a classic two-kidney, one-clip model in rats, Rhaleb et al. administered Ac-SDKP (400 µg/kg/day, subcutaneously). While blood pressure and cardiac hypertrophy remained elevated, treatment with the peptide significantly reduced both inflammatory and proliferating cells in the myocardium. Importantly, it normalized the interstitial collagen fraction, lowering it from about 10.1%in hypertensive rats to about 5.4%, a level almost identical to that in control animals (≈5.3%). In short, it attenuated detrimental tissue changes even when the pressure overload was unaltered, suggesting a direct role in tissue healing [8].
Additionally, in combination with thymosin-β4, Ac-SDKP promotes tissue repair following myocardial infarction. In a narrative review, Cavasin et al. found that thymosin-β4 promotes both cell migration and cell survival. Its derivative, Ac-SDKP, offers additional benefits by acting as an anti-fibrotic agent in hypertension. In myocardial infarction models, Ac-SDKP has been shown to reverse scar formation and reduce inflammation. It also promoted angiogenesis, as demonstrated in both in vivo and ex vivo studies. Furthermore, Ac-SDKP reduced the risk of cardiac rupture in mice, underscoring its therapeutic potential in cardiovascular repair. Many benefits overlap, suggesting that Ac-SDKP mediates some of the therapeutic action of thymosin β4. However, the researcher mentioned that human studies are still needed to confirm these laboratory and animal findings [9].
In addition, Ac-SDKP reduces the activity of tissue degrading enzymes triggered by IL-1β. In adult rat cardiac fibroblasts, Rhaleb et al. showed that interleukin-1β (IL-1β), a pro-inflammatory cytokine,significantly increased the expression of matrix metalloproteinases (MMP-2, MMP-9 and MMP-13). These enzymes degrade extracellular matrix components and contribute to adverse remodeling. Ac-SDKP did not alter the basal expression of MMPs. However, it strongly inhibited the IL-1β-induced increase in the levels of these enzymes. At the same time, Ac-SDKP increased the expression of tissue inhibitors of metalloproteinases (TIMP-1 and TIMP-2), natural inhibitors of MMP activity. This helped restore the balance of matrix turnover. Ac-SDKP also reduced the activation of two major signaling pathways that drive inflammation and proliferation: NF-κB and ERK/MAPK. Interestingly, IL-1β stimulation did not increase collagen production in this model. Ac-SDKP also had no effect on collagen synthesis. This suggests that its protective role is due to selective rebalancing of tissue remodeling, rather than a general change in collagen production. In conclusion, these results indicate that Ac-SDKP may protect myocardium from pathological remodeling by restoring the balance in matrix regulation [10].
Ac-SDKP protects against autoimmune heart damage in rats. In a model of T-cell-induced myocarditis, Nakagawa et al. treated immunized Lewis rats with Ac-SDKP and observed preservation of cardiac function, both systolic and diastolic. The treatment also reduced cardiac enlargement, reduced scar formation and preserved a healthier myocardial structure. Histological analysis showed a lower number of infiltrating immune cells, including macrophages, dendritic cells and T lymphocytes. In parallel, levels of key inflammatory mediators, including cytokines (IL-1α, TNF-α, IL-2, IL-17), chemokines (CINC-1, IP-10), adhesion molecules (ICAM-1, L-selectin) and matrix metalloproteinases, were significantly reduced. Interestingly, Ac-SDKP did not alter the levels of myosin-specific autoantibodies or antigen-specific T-cell responses. This indicates that its cardioprotective effect is primarily due to a reduction in immune cell recruitment and inhibition of inflammatory mediators, rather than a change in autoantibody production or T-cell activation [11].
Ac-SDKP reduces inflammation and collagen cross-linking in angiotensin II-induced hypertension. González et al. administered angiotensin II to rats for three weeks, and a separate group was treated with Ac-SDKP. Blood pressure and cardiac hypertrophy remained elevated in both groups, but Ac-SDKP prevented increases in both total and cross-linked collagen. This protective effect was attributed to the inhibition of lysyl oxidase (LOX) mRNA and LOXL1 protein, enzymes responsible for collagen cross-linking and scar stiffening.
Furthermore, Ac-SDKP reduced TGF-β expression, inhibited NF-κB activation, and limited lymphocyte infiltration. T CD4⁺ i CD8⁺ and macrophages CD68+ of cardiac tissue. Importantly, the influx of cells T CD4⁺ correlated with LOXL1 expression, suggesting a mechanistic link between immune cell activity and fibrosis. These findings underscore that Ac-SDKP exerts potent anti-fibrotic and anti-inflammatory effects independently of its effects on blood pressure [ 12].In addition, it protects the heart after myocardial infarction in early and late stage mice. Peng et al. administered Ac-SDKP (1.6 mg/kg/day) to C57BL/6J mice after myocardial infarction. In the first week, the treatment reduced the number of fatal wall ruptures, decreased ICAM-1 levels, reduced macrophage influx and gelatin digestion activity, inhibited p53 and reduced myocardial cell death; at the same time, the number of small blood vessels at the edge of the injury increased, suggesting better new vessel growth. At week five, the hearts showed less interstitial collagen, preserved structure, lower levels of endoplasmic reticulum stress (CHOP) and maintained SERCA2 (crucial for calcium metabolism), and overall better function. In short, it reduces early damage and promotes healthier long-term remodeling [13].
In another study, Ac-SDKP reduces cardiac fibrosis and improves relaxation in diabetic cardiomyopathy. Castoldi et al. induced diabetes in rats and, two months later, began administering Ac-SDKP (1 mg/kg/day via minipumps) for eight weeks. Diabetic rats exhibited high sugar levels, pronounced interstitial and perivascular fibrosis, and higher concentrations of cardiac TGF-β1 and phospho-Smad2/3. Ac-SDKP reduced both types of fibrosis and limited TGF-β/Smad signaling, even in animals receiving the ACE inhibitor ramipril. Cardiac ultrasound studies revealed that diabetes impaired systole and diastole; insulin and ramipril restored both functions, whereas Ac-SDKP partially improved diastole (diastolic function). These data highlight antifibrotic benefits with moderate functional improvement in this model [14].
Furthermore, it protects coronary vessels from radiation-induced damage and preserves blood flow. In a rat model of chest irradiation, Sharma et al. administered Ac-SDKP subcutaneously for 18 weeks. Radiation reduced resting blood flow, killed endothelial cells, increased coronary fibrosis, and disrupted tight junction protein function (claudin-1, JAM-2). It restored blood flow to normal, preserved endothelial cells, decreased fibrosis, and restored tight junctions. In vitro studies showed Ac-SDKP enters endothelial cells and lowers radiation-induced reactive oxygen species; in vivo, the labeled peptide accumulated in endothelial cells within a few hours. These findings indicate vascular protection, less oxidative damage, and improved microvascular integrity after irradiation [15].
In addition, it reduces stress-induced scar formation in cardiac support cells. In human cardiac fibroblasts, cells were pretreated with Ac-SDKP (10 nM) and then treated with tunicamycin (0.25 µg/ml), which induces „protein stress” inside the cell factory (endoplasmic reticulum). Ac-SDKP helped stop stressed cells from producing too much collagen. It worked by calming the cells' response to stress, lowering the activity of a stress protein called CHOP, and reducing the activity of an inflammatory switch called NF-κB. It also lowered levels of IL-6, a signal that causes inflammation. When CHOP was genetically reduced, it continued to decrease NF-κB and type I collagen activity at both the protein and mRNA levels, confirming the same pathway [16]. Simply put: under stress conditions, it helps cells avoid excessive production of scar protein.In addition, it reduces inflammation of the vascular lining induced by TNF-α. In human coronary artery endothelial cells, TNF-α stimulation induced a significant increase in ICAM-1 expression.This adhesion molecule plays a key role in promoting leukocyte adhesion to the blood vessel surface. Ac-SDKP pretreatment significantly reduced ICAM-1 levels in a dose-dependent manner. Mechanistic analysis showed that this effect was mediated by inhibition of the IKK → IκB → NF-κB signaling cascade, which is crucial for activating inflammatory gene expression. Interestingly, two other signaling pathways - p38 MAPK and ERK - were unaltered, indicating that Ac-SDKP selectively interacts with the NF-κB pathway to exert anti-inflammatory effects in endothelial cells [17].
Ac-SDKP helps keep blood vessel linings quiescent and reduces their „stickiness” during inflammation. It also prevents large artery scarring in angiotensin II-induced hypertension, even without lowering blood pressure itself. In rats infused with angiotensin II, Ac-SDKP reduced collagen accumulation in the aorta and limited the signals (collagen type I and III mRNA) that cause scarring. It also lowered protein kinase C hyperactivity, oxidative stress, ICAM-1, and macrophage infiltration into the vessel wall. Fibrotic signals dropped (less TGF-β1 and Smad2 activity), while the natural brake on this pathway (Smad7) increased. Blood pressure and aortic thickness remained high, so these benefits to the vessel wall resulted from direct actions on tissues rather than changes in blood pressure [18].
Ac-SDKP also protects the heart from radiation damage. In rats that received targeted thoracic radiation, 18 weeks of Ac-SDKP preserved cardiac function, reduced extracellular matrix accumulation and fibrosis, reduced macrophage influx and decreased cardiac cell death. The level and release of Mac-2 (galectin-3), a macrophage protein responsible for fibrosis, also decreased. Ac-SDKP was observed inside macrophages near the cell nucleus and prevented the radiation-triggered release of Mac-2; when fibroblasts lacked Mac-2, radiation caused much weaker scarring signals [19]. It helps maintain healthier vessels and heart tissue after radiation by reducing inflammation and scar formation.
Ac-SDKP for lung health (based on animal studies)
Ac-SDKP exhibits stronger anti-scarring effects than thymosin-β4 in lung models. Firstly, in laboratory studies using lung cells from individuals with idiopathic pulmonary fibrosis (IPF), it slowed down excessive cell growth and reduced two fibrosis signals induced by TGF-β: α-SMA and collagen. Meanwhile, in mice that were administered
bleomycin to induce lung damage, thymosin-β4 helped in the early stage (day 7)
by reducing inflammation and early scarring, but did not halt fibrosis in
later stages (days 14–21). These findings suggest that Ac-SDKP blocks the early stages
scarring in cells and can provide more stable and long-lasting benefits
anti-fibrotic than its precursor, thymosin-β4 [20]. Furthermore, it inhibits lung scarring
associated with silica by restoring KIF3A and turning off β-catenin signaling. Specifically, in silicosis, KIF3A levels were low in patient samples
in the lungs of rats. After restoring KIF3A activity, β-catenin and its downstream factors
that drive MRTF-A and SRF fell, thereby slowing epithelial-to-myofibroblast transition
(EMyT) associated with scarring. This consistently increased KIF3A function, and as a result
reduced β-catenin/MRTF-A/SRF signaling. However, after KIF3A depletion, Ac-SDKP lost these
benefits, confirming that KIF3A is essential for its anti-fibrotic effect [21].
In another study, Ac-SDKP in combination with VIP ameliorated COPD-related changes caused by
cigarette smoking in mice. It reduced oxidative damage (lower MDA levels) and scarring
(lower hydroxyproline levels) and a key factor causing fibrosis (lower TGF-β levels).
At the same time, the amount of inflammatory cytokines (TNF-α, IL-1β, IL-6) decreased, and protection improved.
antioxidant (higher SOD activity). Correspondingly, lung tissue under a microscope showed
less inflammation and less structural remodeling. The combination of these substances was beneficial
antioxidant, anti-inflammatory, and anti-fibrotic in a model of damage caused by
dymem [22, 23]. Ac-SDKP also showed significant results in both prevention and treatment
bleomycin-induced pulmonary fibrosis. In CD-1 mice, Ac-SDKP (0.6 mg/kg, i.p.) was administered from day 0
or On day 7, it improved survival and reduced bleomycin-associated weight loss. Furthermore, the lungs
showed less swelling and fewer invasive immune cells, a healthier
tissue structure and reduced fibrosis: both collagen staining and levels decreased
soluble collagen. Mechanically, the pro-fibrotic IL signals decreased
17 and TGF-β, α-SMA decreased, indicating fewer myofibroblasts. Importantly, the benefits
appeared in both early (prophylactic) and delayed (therapeutic) schedules
Furthermore, it reduces silica-induced lung fibrosis through the P-HSP27/SNAI1 pathway.
Silica induced an increase of P-HSP27, SNAI1, α-SMA, and collagens I/III in lung tissue.
However, Ac-SDKP—administered before exposure or after the onset of the disease—reduced all these
markers and reduced the number of positive cells for both P-HSP27 and α-SMA in imaging. What
important, administration to healthy control individuals did not alter protein expression, suggesting that its
the action is selective for diseased lungs [25].
Furthermore, it shows strong anti-scarring effects in many animal studies. In a meta-analysis
comprising 18 randomized controlled trials (428 animals, 2008–2021) found that Ac-SDKP reduced
a few signs of fibrosis compared to untreated models: α-SMA (SMD −2.44), collagen type I
(SMD −5.36), type III collagen (SMD −3.07), TGF-β (SMD −2.88), and the surface area of lung nodules
SMD
−1.80); all P<0.001. Furthermore, hydroxyproline—a chemical marker of collagen—also decreased
significant change [SMD 7.62; 95% CI 4.90–10.33; P=0.000], which is consistent with the impact on rotation
collagen. These results indicate that Ac-SDKP consistently slows fibrosis in disease models
lungs [26]. In another study, it lowered TGF-β and CTGF levels, inhibiting lung scarring associated with
silica in rats. Rats were administered silica to induce fibrosis, and then
prophylactically or therapeutically Ac-SDKP (800 µg/kg/day). Compared to the control group
silicosis, significant reduction in TGF-β1 protein levels was observed in the treated lungs (to ~0.244 ±
0.016) and CTGF (up to ~0.241 ± 0.017). Similarly, mRNA levels decreased, and CTGF mRNA was particularly lower compared to the model groups (P<0.05). In the group
prophylactic both protein and mRNA for TGF-β1 were significantly below the level at 8 weeks
silica model (P<0.05). Finally, lung histology confirmed less fibrosis [27]. Furthermore
it inhibits collagen buildup and improves lung structure in silicosis. Rats exposed to
silica treatment received Ac-SDKP either after injury (treatment) or 48 hours before exposure
(prevention). In treated groups, compared to silicosis models, the surface area of silicotic nodules
fell to 84.28%and 67.93%, hydroxyproline to 70.89%and 58.18%, type I collagen to 71.08%and 58.13%, and
Type III collagen up to 80.13% and 70.70% (at respective time points). In the prophylactic groups,
compared to the 8-week silicosis model, nodules were reduced by 61.13%, hydroxyproline by
60.27%, and type I and III collagen up to 40.13%and 65.77%. The HE and VG staining, respectively, showed
milder fibrosis. This reduced both collagen content and visible scarring [28].
Additionally, it protects the lungs and bones by calming macrophage pathways upon exposure to
silica. In rats and cell models, silica activated TLR4 and RANKL, causing
pneumonia and bone resorption by osteoclasts. In contrast, Ac-SDKP treatment inhibited signaling
TLR4 and RANKL protected lung elastin, reduced lung inflammation, and limited activation
macrophages. Simultaneously, in the bones Ac-SDKP blocked osteoclast differentiation and helped
maintain bone density and microarchitecture. These results indicate a double protection: healthier lungs and
more stable bones in diseases related to silica [29]. It also reduces scarring
lungs, inhibiting the maturation of cells forming scars. TGF-β1 typically stimulates lung support cells
(fibroblasts) to transform into myofibroblasts and produce additional collagen. After administration
Ac-SDKP decreased α-SMA and collagen levels while also reducing TGF-β1 and its receptor levels.
lowered. Then, in rats with silica-induced lung injury, administration of Ac-SDKP before
or after exposure, it reduced TGF-β1 levels, RAS signaling, and SRF activity, and decreased the number
positive α-SMA myofibroblasts in pulmonary nodules. As a result, the accumulation decreased
collagen, which has shown protection against fibrosis [30, 31]. Furthermore, Ac-SDKP protects the lining
lung alveoli, preventing epithelial cells from transforming into the cells that form
scars. Under the influence of damage signals, such as silica and TGF-β1, the level of markers decreases
epithelial (E-cadherin, SP-A), while mesenchymal markers increase
fibrosis (vimentin, α-SMA, collagen I/III). Ac-SDKP reversed this harmful change:
epithelial identity was preserved, fibrosis markers decreased, and the TGF-β1/ROCK1 pathway was
weakened. Therefore, the delicate surface of the lung alveoli remained closer to normal and
less susceptible to scarring [32]. Furthermore, it alleviates stress on the „protein factory” and cell death in
lung vesicle cells, which in turn reduces lung scarring. When silica strikes,
The cells show high ER stress signals (GRP78, phosphorylated PERK and eIF2α), CHOP, and caspase-
12, and many cells die. Thanks to Ac-SDKP—similar to the ER stress blocker 4-PBA—these markers
stress decreased, cell death decreased in cell tests and in rats, and collagen in the lungs
has decreased. Overall, by calming the PERK/eIF2α/CHOP pathway and caspase-12, Ac-
SDKP helps protect the epithelial layer and slows the progression of fibrosis [33].H2. Ac-SDKP for Kidney Health (Based on Animal Studies)
Ac-SDKP protects the kidneys in lupus without lowering blood pressure. Nakagawa et al. (2017)
demonstrated that in (autoimmune disease)-prone NZBWF1 mice, the renal filters (less sclerosis
glomeruli) and reduced overall damage, without simultaneously lowering systolic
blood pressure. The onset of severe hypertension, albumin in urine, and premature death
occurred later when using Ac-SDKP, but these delays were not statistically significant
This substance also protects kidney function during salt stress. Worou et al. (2015)
They examined Dahl salt-sensitive rats, which were treated for six weeks with a dose of 800 or 1600
µg/kg/day. Blood pressure continued to increase due to the salt diet, but the kidneys showed less
inflammation, less fibrosis, and healthier filters. Only a higher dose reduced the albumin level in
in salt-sensitive rats. In the case of a more resistant strain (SS13BN), both doses
prevented albumin leakage and structural damage [35]. This indicates that the protective effect
it was independent of blood pressure. The peptide also reduces kidney damage caused by
immune system in the case of lupus. Liao et al. (2015) found that within 20 weeks of treatment
Mice susceptible to lupus had better kidney function, even though lupus autoantibody levels did not
changed. Kidneys contained fewer invasive immune cells, such as macrophages, and
T cells. Inflammatory signals such as cytokines and chemokines were lower, and complement protein activation
(C5–9), RANTES, MCP-5, and ICAM-1 were inhibited. As a result, filtration function was preserved and
microscopic damage was reduced [36].
In another study, it prevents kidney damage associated with hypertension despite
persistent high blood pressure. Rhaleb et al. (2011) showed that in mice treated with salt
DOCA Ac-SDKP (800 µg/kg/day for 12 weeks) reduced kidney scarring (collagen).,
the expansion of the filtration matrix and the influx of monocytes/macrophages, while blood pressure
remained elevated. Importantly, the urine albumin level normalized—from 41 ± 5 µg to 13 ±
3 µg per 10 g body weight per day, approaching the control level—and the loss of nephrin (a key
filter slit proteins) was partially restored [37]. Therefore, Ac-SDKP protected
filtration barrier and reduced scarring regardless of blood pressure. Furthermore, it protects against scarring and
diabetic kidney dysfunction. Shibuya et al. (2005) showed that in diabetic db/db mice
two eight-week administrations of Ac-SDKP using minipumps resulted in approximately a three-fold
an increase in plasma Ac-SDKP levels without changes in blood glucose. As a result, it was prevented
glomerular edema, mesangial matrix expansion, and accumulation of
extracellular matrix, and plasma creatinine concentration approached normal. Albuminuria
also decreased, though this decrease was not statistically significant. Mechanically it blocked
Smad3 before entering the cell nucleus, thereby reducing TGF-β/Smad signaling
associated with fibrosis [38]. Furthermore, Ac-SDKP reduces kidney scarring in diabetes and represents
additional benefit compared to ACE inhibition. Castoldi et al. (2013) induced diabetes in
rats, and then administered Ac-SDKP (1 mg/kg/day), ramipril (3 mg/kg/day), both drugs together, or
placebo. In untreated diabetic rats, high blood sugar was observed first, higher
urinary albumin (albuminuria), renal fibrosis, and decreased nephrin levels in glomeruli. When used
samego Ac-SDKP, renal fibrosis decreased, but albuminuria did not improve. In the case of
when ramipril was used, both albuminuria and fibrosis decreased, and the level of nephrin
restored. Importantly, the combination of Ac-SDKP with ramipril resulted in a greater reduction of fibrosis than ramipril alone
ramipril, although albuminuria did not improve further. Ac-SDKP reduces fibrosis in nephropathy
diabetic and strengthens the anti-fibrotic protection of ACE inhibitors without additional benefits in
in the range of albuminuria [39].
Interestingly, Zhang et al. (2022) developed a biomimetic dual-network hydrogel composed of
gelatin and curcumin-zinc, coated with DOPA and functionalized with immobilized Ac-SDKP. This system
was designed to overcome the limitations of free drugs, including poor solubility,
absorption and stability. In vivo application in partially nephrectomized rat kidneys
showed that the hydrogel consistently reduced local fibrosis, promoted angiogenesis, and
stimulated the formation of new renal tubules. Material studies confirmed adequate
porosity, mechanical strength, and biocompatibility, which further confirms its potential
therapeutic [40]. Comparative studies also highlight clear and stage-dependent effects
thymosin-β4 (Tβ4). Zuo et al. (2013) used models of unilateral ureteral obstruction in
wild-type mice and PAI-1 knockout mice for evaluation of Ac-SDKP, Tβ4, and Tβ4 in combination with
prolyl oligopeptidase (POP) inhibitor. Ac-SDKP consistently reduced fibrosis in both
genotypes, which showed lower deposition of collagen and fibronectin, a smaller number of activated
myofibroblasts and macrophages, and reduced profibrotic signaling [41]. In addition, Wang and
wsp. (2010) demonstrated that Ac-SDKP inhibited kidney inflammation and fibrosis induced by obstruction.
14-day treatment reduced scarring in rats with unilateral ureteral obstruction
cell-rich and inflammatory changes in histological examination. The peptide reduced macrophage infiltration
renal (ED-1) and reduced the levels of MCP-1, NF-κB, α-SMA, and TGF-β1 proteins in cells
tubular and interstitial. MCP-1 and TGF-β1 gene expression also decreased, which
indicates that this reduced both the migration of inflammatory factors and matrix activation
extracellular, which are key factors causing kidney fibrosis [42]. Further
The evidence comes from models of hypertension with chronic kidney damage. Liao et al.
(2010) administered Ac-SDKP at a dose of 800 µg/kg/day to rats after 5/6 nephrectomy, before injury
(prevention) or after insult (reversal). Despite persistent hypertension and left
heart chambers, treatment reduced albuminuria, limited macrophage infiltration, and lowered the level
kidney collagen in both groups. Loss of nephrin in the renal glomeruli was also partially
preserved or restored, suggesting an improvement in the integrity of the filtration barrier. These findings
they emphasize that the peptide provided kidney protection in both early and advanced stages
diseases, primarily through anti-inflammatory and anti-fibrotic action, rather than through control
blood pressure [43].
In the case of salt-sensitive hypertension, the peptide reduced scarring in both the heart and
in nephrectomy, without affecting blood pressure. Peng et al. (2001) studied rats with one kidney removed,
aldosterone and salt were administered for six weeks. This treatment elevated blood pressure, enlarged the heart, and
kidneys and increased the amount of scar tissue (collagen) along with cell proliferation markers (PCNA).
Administration of Ac-SDKP, especially at the higher dose of 800 µg/kg/day, significantly reduced the amount of collagen and
PCNA in a dose-dependent manner. Importantly, blood pressure and organ enlargement remained
unchanged, while a lower dose (400 µg/kg/day) provided partial benefit [44]. In
In cases of autoimmune kidney diseases, the peptide improved kidney function and reduced
fibrosis. Omata et al. (2006) treated rats with anti-GBM nephritis, starting 14
days after the onset of the disease, administering Ac-SDKP at a dose of 1 mg/kg/day for four weeks.
compared to untreated animals, it reduced protein levels in the urine and decreased urea concentration
in plasma creatinine and improved creatinine clearance. Tissue analysis showed less sclerosis
renal glomeruli and interstitial fibrosis. Mechanically, it reduced
fibronectin, collagen, and TGF-β1 levels, reduced Smad2 signaling, increased Smad7, and decreased
macrophage accumulation in kidney tissue [45]. In diabetes, the peptide blocked kidney scarring,
preventing blood vessel cells from turning into scar-forming cells. Nagai et al.
(2014) demonstrated that Ac-SDKP restored natural protective pathways, including let-7 microRNA and signaling
FGF receptor, which were inhibited by diabetes. As a result, it reduced fibrosis and
epithelial-to-mesenchymal transition (EndMT). Importantly, combining it with an ACE inhibitor improved
kidney protection even more than ACE inhibition itself [46].
In another study, the peptide restored healthy kidney metabolism and reduced fibrosis. Srivastava et al.
(2020) compared ACE inhibitors, ARBs, Ac-SDKP, and their combinations in diabetic mice. They blocked
also its natural formation using a prolyl oligopeptidase inhibitor (POPi). Results
showed that Ac-SDKP mediates the action of ACE inhibitors through reprogramming
kidney metabolism: SIRT3 restored, mitochondrial fatty acid oxidation improved and
impaired glucose utilization was reduced. However, POPi lowered natural levels,
accelerated fibrosis and disturbed metabolic balance. Importantly, ACE inhibitors (but not ARBs)
has partially restored his level and reduced fibrosis. Both ACE inhibitors and Ac-SDKP
reduced mesenchymal transitions and decreased levels of collagen I and fibronectin in the kidneys
diabetic [47].
In cancer therapy, the analog Ac-SDKP helped preserve blood cells during chemotherapy. Carde and
wsp. (1992) tested seraspenide in a phase I–II double-blind, crossover trial with 53
patients receiving cytarabine or ifosfamide. Compared to control periods, patients treated
In research, seraspimod has shown better protection of peripheral blood cells from chemotherapy toxicity. It was
well tolerated and did not exhibit any adverse effects. These results suggest that peptides
Similar to Ac-SDKP, [48] these can protect bone marrow during cytotoxic treatment. In another
peptides did not reduce blood toxicity, but were safe. Cappelaere et al. (1995) studied
84 patients with advanced squamous cell carcinoma receiving carboplatin and continuous dosing
5-fluorouracil, along with placebo or goralatide (Ac-SDKP) at a dose of 12.5 or 62.5 µg/kg/day. Over 221 chemotherapy cycles
No differences were found in the lowest blood morphology values for leukocytes, granulocytes, and platelets.
blood or hemoglobin between groups. The duration of toxicity also remained unchanged. However
anemia and lymphopenia were more frequent with goralatide. Overall, the drug
was well tolerated, but at these doses did not prevent blood cell loss associated with
chemotherapy [49].
In both type 1 and type 2 diabetes, the peptide improved kidney scarring and function. Nitta and
wsp. (2016) treated mice with streptozotocin-induced type 1 diabetes and db/db mice with
type 2 diabetes, using Ac-SDKP, imidapril (an ACE inhibitor), or both drugs together orally. Treatment
oral, both alone and in combination, reduced renal glomerular sclerosis and
tubulointerstitial fibrosis. Plasma cystatin C concentration, which is elevated in diseases
The count has returned to normal levels. All therapies have restored the suppressed microRNAs.
antifibrotic (miR-29 and let-7), with the greatest improvement observed in the group
receiving combination therapy. The peptide concentration in the urine was highest in the group receiving
combination therapy, which indicates an improvement in systemic exposure [50]. In the case of diseases
nephritis of immunological origin lowered the level of protein in urine and reduced inflammation and
fibrosis. Tan et al. (2012) administered 1.0 mg/kg/day to MRL/lpr lupus mice for 8 weeks. In
compared to untreated lupus mice, mice receiving the peptide had less proteinuria and
improved kidney function. Kidney tissue contained fewer infiltrating T cells and macrophages. Under
mechanically, there was a decrease in NF-κB activation and TNF-α production, as well as
reduction of pro-fibrotic markers (TGF-β1, α-SMA, and fibronectin). Smad2/3 phosphorylation
was inhibited, and Smad7 increased. Importantly, the deposition of complexes did not change
immunological and anti-dsDNA antibody levels, suggesting that the benefits stemmed rather from
reduction of inflammation and fibrosis than from a change in antibody formation [51].
In cases of obesity and high salt intake, it protected the kidneys by reducing inflammation, fibrosis, and
even blood pressure. Maheshwari et al. (2018) studied Zucker lean (ZL) and Zucker obese (ZO) rats
fed for 8 weeks with a normal salt intake (0.4%) or a high salt intake (4%), with a subgroup
that's how it was received
1.6 mg/kg/day. High salt content worsened kidney inflammation and fibrosis in both groups, with
obese rats showed the most severe macrophage infiltration (87.8 ± 10.8 compared to 19.14
± 1.5 cells/mm² in lean rats). Treatment reduced macrophage infiltration in obese
rats to 32.18 ± 2.4 cells/mm² (P<0.05) and reduced glomerular sclerosis, and
also interstitial fibrosis in both the cortex and medulla (P<0.05). Systolic blood pressure in
obese rats fed salt also decreased from 164 ± 6.9 to 144.05
± 14.1 mmHg (P=0.004). Albuminuria was higher in obese rats than in lean rats, but it did not change
significant change under the influence of salt intake or treatment [52].
Ac-SDKP for brain and nerve health (based on research)
animals)
Protection in models of Parkinson's disease
This peptide helps protect dopamine-producing neurons and supports better motor function and memory in
model of Parkinson's disease. Kamarehei and Zahednasab (2025) were the first to show in experiments
that initial treatment of SH-SY5Y nerve cells with 20 nM of this peptide
protected them from 6-OHDA, a toxin commonly used to mimic Parkinson's disease. In
In rat studies, daily doses of 800 µg/kg after 6-OHDA-induced brain damage preserved
more dopamine neurons and reduced cell death by lowering caspase-3 activity and
caspase-12. Rats treated also showed improved motor coordination and memory
spatial, and fewer symptoms of anxiety and depression. From a mechanical perspective, the benefits resulted from
reduction of oxidative stress, alleviation of endoplasmic reticulum (ER) stress, and reduction of
inflammatory signals in the brain, which supports the survival and regeneration of neurons [53].
Regeneration after spinal cord injury
It also speeds up regeneration and redirects inflammation towards healing after spinal cord injury.
vertebral. Hashemizadeh et al. (2022) administered Wistar rats 0.8 mg/kg subcutaneously once
daily for seven days, starting two to six hours after spinal cord injury
caused by the fall of a weight. Compared to untreated animals, rats subjected to
treatment, they regained better walking ability, lost fewer motor neurons, and had lower levels of
TNF-α (pro-inflammatory signal) and caspase-3. At the same time, the level of CD206 mRNA, a pro-
healing M2 macrophages. Tissue studies showed smaller areas of damage. Overall,
treatment caused a shift in immune response from harmful M1-type activity to
protective M2-type activity, which brought both functional and structural benefits [54].
Protection after traumatic brain injury (TBI)
Ac-SDKP helps protect the brain and aids in its repair when administered soon after injury. Zhang
i wsp. (2017) induced controlled brain cortex injuries in rats and administered this compound (0.8
(mg/kg/day) via minipump for three days, starting one hour after injury. From day 7 to day 35
The results of sensorimotor tests improved, and in days 33–35, spatial learning was also
better compared to the control group (p < 0.05). At the end of the study, the size decreased
damage to the cerebral cortex and loss of hippocampal neurons, while an increase in blood vessels,
The creation of new neurons and dendritic spine density were greater. Early treatment
it also reduced fibrin accumulation and attenuated immune cell activation. Tests
Mechanistic studies have shown that blocking TGF-β1/NF-κB signaling largely explains the effect
anti-inflammatory [55].
Benefits in a disease similar to multiple sclerosis (MS)
It also reduces brain stress and inflammation in multiple sclerosis models. Pejman et al.
(2020) C57BL/6 mice were subjected to experimental autoimmune encephalomyelitis
vertebral (EAE). Usually EAE increases ER stress markers (caspase-12, CHOP, PDI), stress
oxidative stress and immune cell infiltration into the hippocampus. Treatment with caspase-12 and
CHOP in oligodendrocytes decreased, caspase-3 activation decreased, ROS oxidation decreased, and
lipid peroxidation, antioxidant capacity improved, and IL-6/IL-1β levels decreased.
Brain fragments confirmed smaller hippocampal damage and less cell infiltration.
immune protection, indicating a slower disease progression [56].
Ac-SDKP for liver health (based on research)
animals)
Slowing down the process of liver scarring caused by chemicals
The peptide Ac-SDKP helps protect the liver from chemical damage by regulating
key gene control switch and growth pathway. Wei et al. (2022) studied rats with damage
carbon tetrachloride-induced liverCarbon tetrachlorideand found less death of star-shaped cells —
main cells that form scars in the liver. Fibrosis also decreased. Tests
Mechanistic studies have shown that the treatment reduced WTAP levels, an enzyme that adds the m6A mark. m⁶A do
RNA. This change stabilized Ptch1 RNA and adjusted the activity of the Hedgehog pathway, a major
factor causing scar formation. Overall, the results highlight the action
anti-fibrotic via the WTAP/m pathway⁶A/Ptch1, which regulates Hedgehog signaling [59].
H3. Protection against fibrosis caused by bile duct obstruction
Ac-SDKP also protects the liver when scarring is caused by bile duct obstruction.
Zhang et al. (2012) used a bile duct ligation (BDL) model in rats and
treated them continuously for two weeks. Compared to untreated animals, those that
received the peptide, had inhibited TGF-β1 signaling and lower levels of markers associated with
activated stellar cells (α-SMA, FSP-1). Gene expression also decreased
related to collagen (Col I, Col III) and turnover enzymes (MMP-2, TIMP-1, TIMP-2). Blood markers
liver function tests improved, and ALT, AST, bilirubin, and prothrombin time approached
to the norm. Fewer mast cells were observed in tissue preparations, and they were smaller
collagen accumulation and general reduction of fibrosis and inflammation [60].
H3. Maintaining Natural Defense and Repair Signals
It helps the liver maintain its natural resistance during prolonged chemical damage.
Chen et al. (2010) discovered that with continuous exposure to Carbon tetrachloride natural peptide levels decreased with age
time. Replacing it with infusion (800 µg/kg/day for eight weeks) allowed for the maintenance of levels
output and limit liver damage, inflammation, and fibrosis. Liver enzyme levels
It dropped in the blood, the number of inflammatory cells decreased CD45⁺, and collagen and α-SMA deposits were reduced. Pro-fibrotic signals, such as TGF-β1 and phospho-
Smad2/3 were decreased, while repair-associated signals, BMP-7 and phospho-Smad1/5/8,
increased. In cell tests, it directly blocked the activation of star-shaped cells,
confirming an anti-fibrotic effect at the cellular level [61].
H2. Ac-SDKP for skin and tissue repair (based on research on
(animals) H3. Hydrogel skin adhesive that speeds up healing and
scar-reducing
Special cellulose-based skin glue (Dopa-OCMC-PAA, compared to OCMC-PAA) was
created to carry and release Ac-SDKP. Both versions showed good swelling profiles and
distribution, high mechanical strength and safety of use with cells, but the best
The Dopa-OCMC-PAA results were achieved. In mice with liver bleeding, this glue stopped it faster
bleeding. In fibroblast tests, it raised enzyme levels responsible for remodeling
tissues (MMP-1 and MMP-3), while simultaneously downregulating collagen gene activity. In rabbits with thickened
scarring on the ears Dopa-OCMC-PAA in combination with peptide reduced scar scoring, lowered the number
cells, improved collagen structure, and again showed higher levels of MMP-1/MMP-3 with less
collagen gene activity. In summary, these results showed improved wound healing and reduced scarring [62].
H3. Topical application improves skin survival and repair
In skin flap operations in rats (abdominal and dorsal), injections of Ac-SDKP
dawcze 5 µg/kg twice a day for three days increased the survival of healthy skin. The viable area.
The flap increased from 50.9 ± 19.3% to 66.4 ± 7.5% in the case of the abdominal flaps and from 53.4 ± 4.2% to 74.7 ±
6.6% in the case of dorsal flaps. In the case of skin tissue damaged by UVB radiation
Topical application improved survival. Topical application also accelerated growth.
new skin, increased the level of keratin 14 (a marker of skin-building cells), and increased the level of
fibronectin, demonstrating its role in vascular development and repair [63].
H3. Protecting blood formation during chemotherapy
In mice receiving the chemotherapy drug doxorubicin, administration of Ac-SDKP at a dose of 2.4
µg/day (continuously or divided) starting 48 hours before treatment reduced
mortality and protected stem cells responsible for blood formation (LTRC, CFU-S, HPP-CFC and
CFU-GM). Adding G-CSF further accelerated CFU-GM recovery. Timing was critical.
administrations — to protect against short-term bone marrow damage and long-term cell loss
maternal, it was necessary to start administration before chemotherapy [64].
H3. Stronger anti-fibrotic effect thanks to improved analogs and inhibitor combinations
AceIn lung fibroblast experiments, the ACE-resistant form of Ac-SDKP reduced signals
scarring (TGF-β/Smad3) and collagen accumulation better than the natural form. Abbreviated fragment
(Ac-DKP) had only weak activity and was slowly degraded by ACE. In combination with inhibitors
ACE peptide inhibited hydroxyproline (a collagen marker) more than it did on its own, showcasing stronger
action and clinical potential. In doses from 10⁻⁶ to 10⁻¹⁷ M both thymosin-beta4 (Tβ4) and peptide
reduced mast cell growth (preferably at a dose) 10⁻¹⁴ M ) and caused unusual changes
nuclear cell cycle arrest. At a concentration 10⁻⁸ M they also caused
release of chemicals from mast cells (degranulation), with the peptide showing
a stronger effect (~89%) than Tβ4 (~57%). Other fragments of Tβ4 showed no effect, which
demonstrates that the effect was specific to intact Tβ4 and the peptide [65, 66].
Ac-SDKP Dose
In preclinical studies, Ac-SDKP is most commonly administered subcutaneously via minipump in
doses around 0.8 mg/kg/day to limit fibrosis and inflammation in the heart/vessels and
nerkach. W badaniach na myszach po zawale serca czasami stosuje się dawkę 1,6 mg/kg/dobę w celu
providing early protection. In the brain/nerves in short cycles starting within a few
hours from injury, a dose of approximately 0.8 mg/kg/day is usually administered for 3–7 days. In studies
for cancer, an initial treatment dose of about 10 nM is commonly used. In liver protocols
anti-fibrotic agents are often given at a dose of about 0.8 mg/kg/day during chronic injury. In
In the bleomycin model of lungs, a dose of 0.6 mg/kg was administered intraperitoneally with repeated doses.,
starting from day 0 or day 7. For skin/wound repair, topical dosage
included 5 µg/kg per injection twice daily for 3 days or peptide-containing hydrogels
for local release. In hematology/bone marrow protection, very low doses are used
microgram, such as 2.4 µg/day in mice before chemotherapy and short courses of µg/kg/day in
early clinical trials.References
1. Wang, W., Jia, W., and Zhang, C. (2022). The role of Tβ4-POP-Ac-SDKP axis in organ fibrosis. International journal of molecular sciences, 23(21), 13282. https://doi.org/10.3390/ ijms232113282
2. Nakagawa, P., Romero, C. A., Jiang, X., D’Ambrosio, M., Bordcoch, G., Peterson, E. L., Harding, P., Yang, X. P., & Carretero, O. A. (2018). Ac-SDKP reduces mortality and risk of cardiac rupture after subacute myocardial infarction. PLoS One, 13(1), e0190300. https://doi.org/10.1371/ journal.pone.0190300 https://pubmed.ncbi.nlm.nih.gov/29364896/
3. Peng, H., Carretero, O. A., Brigstock, D. R., Oja-Tebbe, N., and Rhaleb, N. E. (2003). Ac-SDKP reverses cardiac fibrosis in rats with renal vascular hypertension. Hypertension, 42(6), 1164–1170. https://doi.org/10.1161/01.HYP.0000100423.24330.96 https://pubmed.ncbi.nlm.nih.gov/14581293/
4. Yang, F., Yang, X. P., Liu, Y. H., Xu, J., Cingolani, O., Rhaleb, N. E., & Carretero, O. A. (2004). Ac-SDKP reverses inflammation and fibrosis in rat hearts after myocardial infarction. Hypertension, 43(2), 229-236. https://doi.org/10.1161/01.HYP.0000107777.91185.89 https:// pubmed.ncbi.nlm.nih.gov/14691195/
5. Rasoul, S., Carretero, O. A., Peng, H., Cavasin, M. A., Zhuo, J., Sanchez-Mendoza, A., Brigstock, D. R., & Rhaleb, N. E. (2004). Anti-fibrotic effect of Ac-SDKP and inhibition of angiotensin-converting enzyme in hypertension. Journal of Hypertension, 22(3), 593-603. https://doi.org/ 10.1097/00004872-200403000-00023 https://pubmed.ncbi.nlm.nih.gov/15076166/
6. Rhaleb, N. E., Peng, H., Harding, P., Tayeh, M., LaPointe, M. C., & Carretero, O. A. (2001). Effect of N-acetyl-seryl-aspartyl-lysyl-proline on DNA and collagen synthesis in rat heart fibroblasts. Hypertension, 37 (3), 827-832. https://doi.org/10.1161/01.hyp.37.3.827 https://pubmed.ncbi.nlm.nih.gov/11244003/
7. Liu, Y.-H., D'Ambrosio, M., Liao, T.-D., Peng, H., Rhaleb, N.-E., Sharma, U., André, S., Gabius, H.-J. and Carretero, O. A. (2009). N-acetyl-seryl-aspartyl-lysyl-proline prevents cardiac remodeling and dysfunction induced by galectin-3, a lectin that regulates adhesion/growth in mammals. American Journal of Physiology-Heart and Circulatory Physiology, 296(2), H404-H412. https://doi.org/ 10.1152/ajpheart.00747.2008 https://pubmed.ncbi.nlm.nih.gov/19098114/
8. Rhaleb, N. E., Peng, H., Yang, X. P., Liu, Y. H., Mehta, D., Ezan, E. & Carretero, O. A. (2001). Long-term effect of N-acetyl-seryl-aspartyl-lysyl-proline on collagen deposition in the left ventricle of rats with hypertension caused by two-kidney, one-clip renal artery stenosis. Circulation, 103(25), 3136–3141. https://doi.org/10.1161/01.cir.103.25.3136 https://pubmed.ncbi.nlm.nih.gov/11425781/
9. Cavasin M. A. (2006). Therapeutic potential of thymosin beta-4 and its derivative N-acetyl-seryl-aspartyl-lysyl-proline (Ac-SDKP) in the treatment of post-infarction heart. American Journal of Cardiovascular Drugs drugs, devices, and other interventions, 6(5), 305-311. https://doi.org/ 10.2165/00129784-200606050-00003 https://pubmed.ncbi.nlm.nih.gov/17083265/
10. Rhaleb, N. E., Pokharel, S., Sharma, U. C., Peng, H., Peterson, E., Harding, P., Yang, X. P. and Carretero, O. A. (2013). N-acetyl-Ser-Asp-Lys-Pro inhibits matrix metalloproteinase activation by interleukin-1β in cardiac fibroblasts. Pflügers Archiv - European Journal of Physiology, 465(10), 1487-1495. https://doi.org/10.1007/s00424-013-1262-8 https://pubmed.ncbi.nlm.nih.gov/23652767/
11. Nakagawa, P., Liu, Y., Liao, T. D., Chen, X., González, G. E., Bobbitt, K. R., Smolarek, D., Peterson, E. L., Kedl, R., Yang, X. P., Rhaleb, N. E., and Carretero, O. A. (2012). N-acetyl-seryl-aspartyl-lysyl-proline treatment prevents experimental autoimmune myocarditis in rats. American Journal of Physiology-Heart and Circulatory Physiology, 303(9), H1114–H1127. https://doi.org/10.1152/ajpheart.00300.2011 https://pubmed.ncbi.nlm.nih.gov/22923621/
12. González, G. E., Rhaleb, N. E., Nakagawa, P., Liao, T. D., Liu, Y., Leung, P., Dai, X., Yang, X. P. and Carretero, O. A. (2014). N-acetyl-seryl-aspartyl-lysyl-proline reduces cardiac collagen cross-linking and inflammation in rats with angiotensin II-induced hypertension. Clinical Science., 126(1), 85-
13. Peng, H., Xu, J., Yang, X. P., Kassem, K. M., Rhaleb, I. A., Peterson, E., and Rhaleb, N. E. (2019). N-acetyl-seryl-aspartyl-lysyl-proline treatment protects the heart from excessive myocardial damage and heart failure in mice. Canadian Journal of Physiology and Pharmacology, 97(8), 753–765. https://doi.org/10.1139/cjpp-2019-0047 https://pubmed.ncbi.nlm.nih.gov/30998852/
14. Castoldi, G., di Gioia, C. R. T., Bombardi, C., Perego, C., Perego, L., Mancini, M., Leopizzi, M., Corradi, B., Perlini, S., Zerbini, G., and Stella, A. (2009). Prevention of myocardial fibrosis by N-acetyl-seryl-aspartyl-lysyl-proline in diabetic rats. Clinical Science, 118(3), 211– 220. https:// doi.org/10.1042/cs20090234 https://pubmed.ncbi.nlm.nih.gov/20310083/
15. Sharma, U. C., Sonkawade, S. D., Baird, A., Chen, M., Xu, S., Sexton, S., Singh, A. K., Groman, A., Turowski, S. G., Spernyak, J. A., Mahajan, S. D., & Pokharel, S. (2018). Impact of the novel peptide Ac-SDKP on radiation-induced coronary endothelial damage and resting myocardial blood flow. Cardio-Oncology, 4, 8 . https://doi.org/10.1186/s40959-018-0034-1 https://pubmed.ncbi.nlm.nih.gov/31057947/
16. Suhail, H., Peng, H., Matrougui, K. and Rhaleb, N. E. (2024). Ac-SDKP mitigates stress-induced ER
production of collagen in cardiac fibroblasts by inhibiting NF-κB expression
through CHOP. Frontiers in Pharmacology, 15, 1352222.
https://doi.org/10.3389/fphar.2024.1352222 https://pubmed.ncbi.nlm.nih.gov/38495093/
17. Zhu, L., Yang, X. P., Janic, B., Rhaleb, N. E., Harding, P., Nakagawa, P., Peterson, E. L. and Carretero,
O. A. (2016). Ac-SDKP inhibits TNF-α-induced ICAM-1 expression in endothelial cells
by inhibiting IκB kinase and activating NF-κB. American Journal of Physiology-Heart and
Circulatory Physiology, 3109), H1176-H1183. https://doi.org/10.1152/ajpheart.00252.2015
https://pubmed.ncbi.nlm.nih.gov/26945075/
18. Lin, C. X., Rhaleb, N. E., Yang, X. P., Liao, T. D., D’Ambrosio, M. A., & Carretero, O. A. (2008).
Prevention of aortic fibrosis with N-acetylo-seryl-aspartyl-lizyl-proliny in hypertension
induced by angiotensin II. American Journal of Physiology-Heart and Circulatory Physiology, 295(3),
H1253-H1261. https://doi.org/10.1152/ajpheart.00481.2008
https://pubmed.ncbi.nlm.nih.gov/18641275/
19. Sharma, U. C., Sonkawade, S. D., Spernyak, J. A., Sexton, S., Nguyen, J., Dahal, S., Attwood, K. M.,
Singh, A. K., van Berlo, J. H., & Pokharel, S. (2018). The small peptide Ac-SDKP inhibits radiation-induced cardiomyopathy. Circulation: Heart Failure, 11(8), e004867. https://doi.org/
10.1161/CIRCHEARTFAILURE.117.004867 https://pubmed.ncbi.nlm.nih.gov/30354563/
20. Conte, E., Iemmolo, M., Fruciano, M., Fagone, E., Gili, E., Genovese, T., Esposito, E., Cuzzocrea, S. i
Vancheri, C. (2015). Influence of thymosin β4 and its N-terminal fragment Ac-SDKP on human fibroblasts
lung exposed to TGF-β and in a mouse model of bleomycin-induced pulmonary fibrosis.
Expert Opinion on Biological Therapy, 15(Suppl 1), S211–S221. https://doi.org/
10.1517/14712598.2015.1026804 https://pubmed.ncbi.nlm.nih.gov/26098610/
21. Liu, S., Jin, R., Zheng, G., Wang, Y., Li, Q., Jin, F., Li, Y., Li, T., Mao, N., Wei, Z., Li, G., Fan, Y.,
Xu, H., Li, S., & Yang, F. (2023). Ac-SDKP promotes $\beta$-catenin inhibition via KIF3A.
through the ciliary mechanism to limit silica-induced transformation
epithelial-myofibroblastic. Biomedicine & Pharmacotherapy, 166, 115411.
https://doi.org/10.1016/j.biopha.2023.115411 https://pubmed.ncbi.nlm.nih.gov/37651800/
22. Cai, J., Chen, Q., Mehrabi Nasab, E. and Athari, S. S. (2022). Immunomodulatory effects of N-acetyl-
seryl-aspartylo-proliny and vasoactive intestinal peptide on the pathophysiology of chronic obstructive
lung diseases. Fundamental & Clinical Pharmacology, 36(6), 1005–1010. https://
doi.org/10.1111/fcp.12811 https://pubmed.ncbi.nlm.nih.gov/35763864/
23. Wang, J., Qian, Y., Gao, X., Mao, N., Geng, Y., Lin, G., Zhang, G., Li, H., Yang, F., & Xu, H. (2020).
Synthesis and identification of a novel peptide, Ac-SDK(biotin) proline, which can elicit an action
anti-fibrotic in rats with silicosis. Drug design, development and therapy, 14,
4315–4326. https://doi.org/10.2147/DDDT.S262716 https://pubmed.ncbi.nlm.nih.gov/33116418/
24. Conte, E., Fagone, E., Gili, E., Fruciano, M., Iemmolo, M., Pistorio, M. P., Impellizzeri, D., Cordaro, M.,
Cuzzocrea, S., & Vancheri, C. (2016). Preventive and therapeutic action of the N-terminal fragment
Thymosin β4 Ac-SDKP in a bleomycin-induced lung fibrosis model. Oncotarget, 7(23),
33841–33854. https://doi.org/10.18632/oncotarget.8409 https://
https://pubmed.ncbi.nlm.nih.gov/27029074/
25. Cao, W., Yao, S. S., Gong, H. B., Zhu, L. Y., Miao, Z. Y., & Deng, H. J. (2022). Regulatory effect of Ac-
SDKP on the phosphorylated heat shock protein 27/SNAI1 pathway in rats with silicosis. China
Chinese Journal of Industrial Hygiene and Occupational Diseases, 40(2), 90-96. https://doi.org/10.3760/ cma.j.cn121094-
20201218-00702 https://pubmed.ncbi.nlm.nih.gov/35255573/
26. Gong, H. B., Zhang, C. M., Tang, X. Y., Gong, R. B., Miao, Z. Y., & Deng, H. J. (2023). Meta-analysis
Inhibition of lung fibrosis by Ac-SDKP in animal models. Zhonghua Lao Dong Wei
Sheng Zhi Ye Bing Zhi, 41 ( 4 ) , 2 6 2 – 2 7 0 . https://doi.org/10.3760/
cma.j.cn121094-20211115-00565 https://pubmed.ncbi.nlm.nih.gov/37248179/
27. Li, Q., Yang, F., Zhang, L.-J., Yan, J.-B., Chen, P., Li, D.-D. & Wu, K.-F. (2009). [Anti-fibrotic
The action of N-acetyl-seryl-aspartyl-lysyl-proline through the regulation of transforming growth factor expression
[Increase in beta and connective tissue growth factor in rats with silicosis]. Zhonghua Lao Dong Wei
Sheng Zhi Ye Bing Za Zhi, 27(7), 390–394. PMID: 20039536 https://
[PMID: 20039536]28. Yan, J.-B., Zhang, L.-J., & Li, Q. (2008). [Antifibrotic effect of N-acetyl-seryl-aspartyl-lysyl-
[lung nodules in rats with silicosis]. Zhonghua Lao Dong Wei Sheng Zhi Ye Bing Za Zhi, 26(7),
401–405. PMID: 19080377 https://pubmed.ncbi.nlm.nih.gov/19080377/
29. Jin, F., Geng, F., Xu, D., Li, Y., Li, T., Yang, X., Liu, S., Zhang, H., Wei, Z., Li, S., Gao, X., Cai, W.,
Mao, N., Yi, X., Liu, H., Sun, Y., Yang, F., & Xu, H. (2021). Ac-SDKP weakens macrophage activation.
and osteoclast lung cells in rats exposed to silica by inhibiting
TLR4 and RANKL signaling pathways. Journal of Inflammation Research, 14, 1647-1660.
https://doi.org/10.2147/ JIR.S306883 https://pubmed.ncbi.nlm.nih.gov/33948088/
30. Xu, H., Yang, F., Sun, Y., Yuan, Y., Cheng, H., Wei, Z., Li, S., Cheng, T., Brann, D., & Wang, R. (2012).
New anti-fibrotic target Ac-SDKP: Inhibition of myofibroblast differentiation in the lungs
silicotic rats. PLoS One, 7(7), e40301. https://doi.org/10.1371/journal.pone.0040301 https://
pubmed.ncbi.nlm.nih.gov/22802960/
31. Wang, X., Liu, Y., Xu, H., Zhang, X., Li, S., Xu, D., Gao, X., Zhang, L., Zhang, B., Wei, Z., Wang, R.,
Brann, D. & Yang, F. (2016). Acetylated α-tubulin is regulated by N-acetyl-seryl-aspartyl-lysyl-
proline (Ac-SDKP) exerts an anti-fibrotic effect in bleomycin-induced pulmonary fibrosis in rats
through silica. Scientific Reports, 6, 32257. https://doi.org/10.1038/srep32257
https://pubmed.ncbi.nlm.nih.gov/27577858/
32. Deng, H., Xu, H., Zhang, X., Sun, Y., Wang, R., Brann, D., & Yang, F. (2016). Protective effect of Ac-
SDKP in alveolar epithelial cells by inhibiting EMT through the pathway
TGF-β1/ROCK1 in silicosis in rats. Toxicology and Applied Pharmacology, 294, 1-10.
https://doi.org/10.1016/ j.taap.2016.01.010 https://pubmed.ncbi.nlm.nih.gov/26785300/
33. Zhang, L., Xu, D., Li, Q., Yang, Y., Xu, H., Wei, Z., Wang, R., Zhang, W., Liu, Y., Geng, Y., Li, S., Gao,
X. and Yang, F. (2018). N-acetyl-seryl-aspartyl-lysyl-proline (Ac-SDKP) alleviates silicosis fibrosis.
by inhibiting apoptosis of lung alveolar type II epithelial cells through
Endoplasmic reticulum stress. Toxicology and Applied Pharmacology, 350, 1–
10. https://doi.org/10.1016/ j.taap.2018.04.025 https://pubmed.ncbi.nlm.nih.gov/29684394/
34. Nakagawa, P., Masjoan-Juncos, J. X., Basha, H., Janic, B., Worou, M. E., Liao, T. D., Romero, C. A.,
Peterson, E. L. & Carretero, O. A. (2017). The effect of N-acetyl-seryl-aspartyl-lysyl-proline on blood pressure.,
Renal damage and mortality in systemic lupus erythematosus. Physiological Reports, 5(2),
e13084. https://doi.org/10.14814/phy2.13084 https://pubmed.ncbi.nlm.nih.gov/ 28126732/
35. Worou, M. E., Liao, T. D., D’Ambrosio, M., Nakagawa, P., Janic, B., Peterson, E. L., Rhaleb, N. E. et al
Carretero, O. A. (2015). Protective effect of N-acetyl-seryl-aspartyl-lysyl-proline on rat kidneys
salt-sensitive Dahla. Hypertension, 664), 816-822. https://doi.org/10.1161/
HYPERTENSION AHA.115.05970 https://pubmed.ncbi.nlm.nih.gov/26324505/
36. Liao, T. D., Nakagawa, P., Janic, B., D’Ambrosio, M., Worou, M. E., Peterson, E. L., Rhaleb, N. E.,
Yang, X. P. and Carretero, O. A. (2015). N-Acetyl-Seryl-Aspartyl-Lysyl-Proline: Protective mechanisms
mouse model of systemic lupus erythematosus. American Journal of Physiology-Renal
Physiology, 308 (10), F1146-F1154. https://doi.org/10.1152/ajprenal.00039.2015
https://pubmed.ncbi.nlm.nih.gov/25740596/37. Rhaleb, N. E., Pokharel, S., Sharma, U., & Carretero, O. A. (2011). Protective effect of N-acetyl-Ser-
Asp-Lys-Pro for kidneys in rats with deoxycorticosterone acetate-salt-induced hypertension.
Journal of Hypertension, 29(2), 330–338. https://doi.org/10.1097/HJH.0b013e32834103ee
The PubMed ID (PMID) you provided, 21052020, corresponds to a research article. To access the English (US) translation of the abstract for this article, you can visit the provided PubMed link: pubmed.ncbi.nlm.nih.gov/21052020/
38. Shibuya, K., Kanasaki, K., Isono, M., Sato, H., Omata, M., Sugimoto, T., Araki, S., Isshiki, K.,
Kashiwagi, A., Haneda, M., & Koya, D. (2005). N-acetyl-seryl-aspartyl-lysyl-proline prevents
kidney failure and mesangial matrix expansion in db/db diabetic mice. Diabetes, 54(3),
838–845. https://doi.org/10.2337/diabetes.54.3.838 https://pubmed.ncbi.nlm.nih.gov/15734863/
39. Castoldi, G., di Gioia, C. R. T., Bombardi, C., Preziuso, C., Leopizzi, M., Maestroni, S., Corradi, B.,
Zerbini, G. and Stella, A. (2013). Anti-fibrotic action of N-acetyl-seryl-aspartyl-lysyl-proline on
Kidneys in rats with diabetes. American Journal of Nephrology, 37(1), 65-73.
https://doi.org/10.1159/000346116 https://pubmed.ncbi.nlm.nih.gov/23327833/
40. Zhang, R., Hu, Z., Wang, Y., Qiu, R., Wang, G., Wang, L., & Hu, B. (2022). Biomimetic hydrogel with
Double network mitigates kidney fibrosis and promotes its regeneration. Journal of Materials
Chemistry B, 10 (45), 9424-9437. https://doi.org/10.1039/d2tb01939f https://
pubmed.ncbi.nlm.nih.gov/36378134/
41. Zuo, Y., Chun, B., Potthoff, S. A., Kazi, N., Brolin, T. J., Orhan, D., Yang, H.-C., Ma, L.-J., Kon, V.,
Late, T., Rhaleb, N.-E., Carretero, O. A. and Fogo, A. B. (2013). Thymosin β4 and its product
degradation, Ac-SDKP, are new reparative factors in kidney fibrosis. Kidney International,
84(6), 1166–1175. https://doi.org/10.1038/ki.2013.209 https://pubmed.ncbi.nlm.nih.gov/23739235/
42. Wang, M., Liu, R., Jia, X., Mu, S., & Xie, R. (2010). N-acetyl-seryl-aspartyl-lysyl-proline ameliorates inflammation
Inflammation of the kidneys and tubulointerstitial fibrosis in rats. International Journal of Molecular
Medicine, 26 (6), 795-801. https://doi.org/10.3892/ijmm_00000527 https://
pubmed.ncbi.nlm.nih.gov/21042772/
43. Liao, T.-D., Yang, X.-P., D’Ambrosio, M., Zhang, Y., Rhaleb, N.-E., & Carretero, O. A. (2010). N-acetyl-
seryl-aspartyl-lysyl-proline ameliorates kidney damage and dysfunction in spontaneously hypertensive rats
and reduced renal mass: Hypertension Research Council. High blood pressure
Arterial, 552), 459-467. https://doi.org/10.1161/HYPERTENSIONAHA.109.144568
https://pubmed.ncbi.nlm.nih.gov/ 20026760/
44. Peng, H., Carretero, O. A., Raij, L., Yang, F., Kapke, A., & Rhaleb, N. E. (2001). Anti-fibrotic
The effect of N-acetyl-seryl-aspartyl-lysyl-proline on the heart and kidneys in rats with induced hypertension
aldosterone and salt. Hypertension, 37(2 Pt 2), 794-800. https://doi.org/10.1161/01.hyp.37.2.794
https:// pubmed.ncbi.nlm.nih.gov/11230375/
45. Omata, M., Taniguchi, H., Koya, D., Kanasaki, K., Sho, R., Kato, Y., Kojima, R., Haneda, M. and Inomata,
N. (2006). N-acetyl-seryl-aspartyl-lysyl-proline attenuates the progression of renal dysfunction and fibrosis in
WKY rats with diagnosed glomerulonephritis. Journal of the American Society of
Nephrology, 17(3), 674–685. https://doi.org/10.1681/ASN.2005040385
https://pubmed.ncbi.nlm.nih.gov/16452498/
46. Nagai, T., Kanasaki, M., Srivastava, S. P., Nakamura, Y., Ishigaki, Y., Kitada, M., Shi, S., Kanasaki, K.
Koya, D. (2014). N-acetyl-seryl-aspartyl-lysyl-proline inhibits diabetes-related kidney fibrosis and epithelial-to-mesenchymal transition. BioMed Research
International, 2014, 696475. https://doi.org/10.1155/2014/696475
https://pubmed.ncbi.nlm.nih.gov/24783220/
47. Srivastava, S. P., Goodwin, J. E., Kanasaki, K. & Koya, D. (2020). Metabolic reprogramming for
The use of N-acetyl-seryl-aspartyl-lysyl-proline protects against diabetic kidney disease. British Journal
of Pharmacology, 177 (16), 3691-3711. https://doi.org/10.1111/bph.15087 https://
pubmed.ncbi.nlm.nih.gov/32352559/
48. Carde, P., Chastang, C., Goncalves, E., Mathieu-Tubiana, N., Vuillemin, E., Delwail, V., Corbion, O.,
Vekhoff, A., Isnard, F., Ferrero, J. M., et al. (1992). [Seraspenid (acetylSDKP): phase I clinical study
I–II concerning a hematopoiesis inhibitor protecting against the toxicity of cytarabine monochemotherapy
Ifosfamide. Clinical Study C R Acad Sci III, 315(13), 545–550. PMID: 1300237 https://
pubmed.ncbi.nlm.nih.gov/1300237/
49. Cappelaere, P., Hecquet, B., Rolland, F., Meeus, L., Domenge, C., Krakowski, I., De Gislain, C.,
Chauvergne, J., Dufour-Esquerré, F., Carde, P. (1995). [Randomized placebo-controlled study on
bone marrow protection with goralatide in patients with upper aerodigestive tract squamous cell carcinoma
respiratory and gastrointestinal tract or esophagus, treated with a combination of carboplatin and
fluorouracil. Bull Cancer, 82(9), 732-737. PMID: 8535033 https://pubmed.ncbi.nlm.nih.gov/8535033/
50. Nitta, K., Shi, S., Nagai, T., Kanasaki, M., Kitada, M., Srivastava, S. P., Haneda, M., Kanasaki, K. i
Koya, D. (2016). Oral administration of N-acetyl-seryl-aspartyl-lysyl-proline alleviates kidney disease in
mice with type 1 and type 2 diabetes through a therapeutic regimen. BioMed Research International,
2016 , 9172157 . https://doi.org/10.1155/2016/9172157 https://
pubmed.ncbi.nlm.nih.gov/27088094/
51. Tan, H., Zhao, J., Wang, S., Zhang, L., Wang, H., Huang, B., Liang, Y., Yu, X. and Yang, N. (2012). Ac-
SDKP ameliorates the progression of lupus nephritis in MRL/lpr mice. International
Immunopharmacology, 14(4), 401–409. https://doi.org/10.1016/j.intimp.2012.07.023https://
pubmed.ncbi.nlm.nih.gov/22922317/
52. Maheshwari, M., Romero, C. A., Monu, S. R., Kumar, N., Liao, T. D., Peterson, E. L., and Carretero,
O. A. (2018). Renal protective effects of N-acetyl-seryl-aspartyl-lysyl-proline (Ac-SDKP) in obese rats
on a high-salt diet. American Journal of Hypertension, 31(8), 902-909. https://doi.org/
10.1093/ajh/hpy052 https://pubmed.ncbi.nlm.nih.gov/29722788/
53. Kamarehei, M., & Zahednasab, H. (2025). Neuroprotective effects of Ac-SDKP peptide in cells
SH-SY5Y and Parkinson's disease rat model against induced oxidative stress
by 6-OHDA and ER stress. Neuropeptides, 112, 102534. https://doi.org/10.1016/j.npep.2025.102534
https:// pubmed.ncbi.nlm.nih.gov/40544680/
54. Hashemizadeh, S., Pourkhodadad, S., Hosseindoost, S., Pejman, S., Kamarehei, M., Badripour, A.,
Omidi, A., Pestehei, S. K., Seifalian, A. M. & Hadjighassem, M. (2022). The peptide Ac-SDKP improves
Recovery of function after spinal cord injury in a preclinical model. Neuropeptides, 92, 102228.
https://doi.org/10.1016/j.npep.2022.102228 https://pubmed.ncbi.nlm.nih.gov/ 35101843/
55. Zhang, Y., Zhang, Z. G., Chopp, M., Meng, Y., Zhang, L., Mahmood, A. i Xiong, Y. (2017). Treatment
traumatic brain injury in rats using N-acetylo-seryl-aspartyl-lizyl-proliny. Journal of Neurosurgery, 126(3), 782-795. https://doi.org/10.3171/2016.3.JNS152699 http://
PubMed
56. Pejman, S., Kamarehei, M., Riazi, G., Pooyan, S., & Balalaie, S. (2020). Ac-SDKP mitigates the progression
experimental autoimmune encephalomyelitis by inhibiting ER stress
oxidative stress in the hippocampus of C57BL/6 mice. Brain Research Bulletin, 154, 21–31.
https://doi.org/10.1016/j.brainresbull.2019.09.014 https://pubmed.ncbi.nlm.nih.gov/31589901/
57. Zhang, L., Chopp, M., Teng, H., Ding, G., Jiang, Q., Yang, X. P., Rhaleb, N. E., & Zhang, Z. G. (2014).
Combination therapy of N-acetyl-seryl-aspartyl-lysyl-proline and tissue plasminogen activator
provides strong neuroprotection in rats after stroke. Stroke, 45(4), 1108–1114. https://
doi.org/10.1161/STROKEAHA.113.004399 https://pubmed.ncbi.nlm.nih.gov/24549864/
58. Kim, D. H., Moon, E.-Y., Yi, J. H., Lee, H. E., Park, S. J., Ryu, Y.-K., Kim, H.-C., Lee, S. and Ryu, J.
H. (2015). Thymosin beta 4 peptide fragment enhances hippocampal neurogenesis and facilitates memory
spatial. Neuroscience, 310, 51-62. https://doi.org/10.1016/j.neuroscience.2015.09.017
https://pubmed.ncbi.nlm.nih.gov/26363149/
59. Wei, A., Zhao, F., Hao, A., Liu, B., & Liu, Z. (2022). N-acetyl-seryl-aspartyl-lysyl-proline (AcSDKP)
mitigates liver fibrosis via the WTAP/m6A/Ptch1 axis through the Hedgehog pathway. Gene, 813,
146125. https://doi.org/10.1016/j.gene.2021.146125 https://pubmed.ncbi.nlm.nih.gov/34921949/
60. Zhang, L., Xu, L. M., Chen, Y. W., Ni, Q. W., Zhou, M., Qu, C. Y., & Zhang, Y. (2012).
Anti-fibrotic effect of N-acetyloxy-seryl-aspartyl-lysyl-proline on liver fibrosis
induced by bile duct ligation in rats. World Journal of Gastroenterology, 18(37),
5283–5288. https://doi.org/10.3748/wjg.v18.i37.5283 https://pubmed.ncbi.nlm.nih.gov/23066324/
61. Chen, Y. W., Liu, B. W., Zhang, Y. J., Chen, Y. W., Dong, G. F., Ding, X. D., Xu, L. M., Pat, B.,
Fan, J. G. & Li, D. G. (2010). Baseline AcSDKP levels attenuate fibrosis.
Carbon tetrachloride-induced liver injury in rats. Journal of Hepatology, 53(3), 528-536.
https://doi.org/10.1016/ j.jhep.2010.03.027 https://pubmed.ncbi.nlm.nih.gov/20646773/
62. Ameri, Z., Shahabi, A., Farsinejad, A., Sattarzadeh Bardsiri, M., Javedani, H., Bagher, Z., Saraee, A. i
Brouki Milan, P. (2025). Adhesive cellulose-based hydrogel containing N-acetyl-seryl- peptide
aspartyl-lysyl-proline for accelerated wound healing and scar prevention in
model of rabbit ears with scars in vivo. International Journal of Biological Macromolecules, 322(Patient
1), 144981. https:// doi.org/10.1016/j.ijbiomac.2025.144981
https://pubmed.ncbi.nlm.nih.gov/40480579/
63. Fromes, Y., Liu, J. M., Kovacevic, M., Bignon, J., & Wdzieczak-Bakala, J. (2006). Acetyl-tetrapeptide-
seryno-asparaginylo-lizylo-prolina improves skin flap survival and accelerates wound healing.
Wound Repair and Regeneration, 14 (3), 306-312. https://doi.org/10.1111/ j.1743-
6109.2006.00125.x https://pubmed.ncbi.nlm.nih.gov/16808809/
64. Massé, A., Ramirez, L. H., Bindoula, G., Grillon, C., Wdzieczak-Bakala, J., Raddassi, K., Deschamps
de Paillette, E., Mencia-Huerta, J. M., Koscielny, S., Potier, P., Sainteny, F. and Carde,
P. (1998). The tetrapeptide acetyl-N-Ser-Asp-Lys-Pro (Goralatide) protects against toxicity induced by
by doxorubicin: improved survival in mice and protection of bone marrow stem cells
bone and progenitor cells. Blood, 91(2), 441-449. PMID: 9427696
https://pubmed.ncbi.nlm.nih.gov/9427696/65. Ramasamy, V., Ntsekhe, M., & Sturrock, E. (2021). Investigation of anti-fibrotic potential
peptides with the sequence N-acetyl-seryl-aspartyl-lysyl-proline. Clinical and Experimental
Pharmacology and Physiology, 48(11), 1558–1565. https://doi.org/10.1111/1440-1681.13565
https://pubmed.ncbi.nlm.nih.gov/34347311/
66. Leeanansaksiri, W., DeSimone, S. K., Huff, T., Hannappel, E., and Huff, T. F. (2004). Thymosin beta
4 and its N-terminal tetrapeptide, AcSDKP, inhibit proliferation and induce dysplastic,
non-apoptotic nuclei and mast cell degranulation. Chemistry & Biodiversity, 1(7), 1091–
1100. https://doi.org/10.1002/cbdv.200490081 https://pubmed.ncbi.nlm.nih.gov/17191900/