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| 1mg |
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| 5mg |
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| 10mg |
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| Targets |
Angiotensin-Converting Enzyme (ACE). Ac-SDKP is a specific substrate for the N-terminal active site of ACE, which degrades the tetrapeptide. By acting as a substrate, it can modulate the activity of ACE. However, its biological activity (anti-proliferative, anti-inflammatory) is mediated not by ACE inhibition but through interaction with a yet-to-be-identified specific receptor, possibly a member of the G-protein-coupled receptor (GPCR) family.
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| ln Vitro |
N-Acetyl-Ser-Asp-Lys-Pro is particularly destroyed by ACE, and upon receiving ACE inhibitor medication, its plasma level increases significantly. Rat cardiac fibroblasts treated with N-Acetyl-Ser-Asp-Lys-Pro exhibit a considerable suppression of cell cycle progression from G0/G1 phase to S phase, as demonstrated by flow cytometry. Moreover, cardiac fibroblasts treated with N-Acetyl-Ser-Asp-Lys-Pro exhibit decreased Smad2 phosphorylation and nuclear translocation[1]. N-acetyl-seryl-aspartyl-lysyl-proline acts only on quiescent progenitors and seems to do this role by inhibiting the activity of a proliferation stimulator specific to stem cells[2]. Collagenase expression is inhibited by N-acetyl-Ser-Asp-Lys-Pro, and activation is linked to higher TIMP-1 and TIMP-2 expression. The IL-1β-mediated increase in MMP-2 and MMP-9 activity as well as MMP-13 expression is normalized by N-Acetyl-Ser-Asp-Lys-Pro[3].
In vitro, Ac-SDKP (TFA) significantly inhibits the proliferation of hematopoietic stem cells. In rat cardiac fibroblasts, treatment with Ac-SDKP shows significant inhibition of the progression of cells from the G0/G1 to the S phase of the cell cycle. It also decreases the phosphorylation and nuclear translocation of Smad2, a key transcription factor in the TGF-beta signaling pathway. Furthermore, it inhibits collagenase expression and activity. |
| ln Vivo |
N-Acetyl-Ser-Asp-Lys-Pro inhibits inflammatory cell infiltration, collagen deposition, nephrin downregulation, and albuminuria caused by hypertension, all of which can cause renoprotection in hypertensive mice[4].
Ac-SDKP TFA has demonstrated significant in vivo activity in hypertensive mouse models. It prevents hypertension-induced inflammatory cell infiltration, collagen deposition, nephrin downregulation, and albuminuria, leading to renoprotection. These anti-fibrotic and anti-inflammatory effects make it a candidate for treating cardiovascular and renal diseases. |
| Enzyme Assay |
Non-cellular assays for Ac-SDKP mainly involve measuring its hydrolysis by purified ACE. Recombinant human ACE protein is incubated with varying concentrations of Ac-SDKP in a reaction buffer (e.g., 50 mM HEPES, 300 mM NaCl, 10 uM ZnCl2, pH 7.5) at 37degC. The reaction is stopped by adding an acid solution. The amount of free product (Ser-Asp-Lys-Pro) or the loss of the substrate is quantified by HPLC or LC-MS, and the kinetic parameters (Km, Vmax, Kcat) for the enzymatic hydrolysis are determined.
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| Cell Assay |
For in vitro cellular assays, rat cardiac fibroblasts are typically used. Cells are serum-starved to synchronize them and then treated with Ac-SDKP (e.g., at 1 microM). After a 24-hour incubation, cells are harvested, stained with propidium iodide (PI), and the cell cycle distribution is analyzed by flow cytometry. The percentage of cells in the G0/G1, S, and G2/M phases is determined. For signaling studies, cells are lysed and protein expression (e.g., phosphorylated Smad2, total Smad2) is analyzed by Western blotting.
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| Animal Protocol |
The in vivo efficacy of Ac-SDKP is often studied in a mouse model of hypertension. For example, male C57BL/6 mice are infused with angiotensin II (e.g., 1.5 mg/kg/day) via osmotic minipump to induce hypertension. Ac-SDKP TFA is co-infused at a rate of 400 microg/kg/day. After 14 days, the mice are euthanized. Kidneys are collected for histology (e.g., PAS staining to assess glomerular injury, collagen staining to assess fibrosis) and for biochemical assays (e.g., measurement of albuminuria, quantification of pro-inflammatory cytokines by ELISA).
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| ADME/Pharmacokinetics |
Ac-SDKP is an endogenous peptide, and its pharmacokinetic (PK) properties are characterized by a very short half-life (t1/2) in plasma, typically only a few minutes, as it is rapidly degraded by ACE. Its plasma concentration is therefore highly dynamic and depends on the balance between its production and its degradation by ACE. In fact, plasma levels of Ac-SDKP rise substantially during ACE inhibitor therapy.
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| Toxicity/Toxicokinetics |
As an endogenous tetrapeptide, Ac-SDKP is generally considered safe. The TFA salt form is a research chemical that can be used at low doses. Toxicological data from clinical development of Ac-SDKP analogs would be required for any pharmaceutical use, but as a research tool, it is handled under standard laboratory precautions. No significant acute toxicity has been reported in peer-reviewed literature for the peptide itself.
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| References |
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| Additional Infomation |
The primary physiological role of Ac-SDKP appears to be a negative feedback regulator of the hematopoietic stem cell niche and a protector against tissue fibrosis. By blocking the TGF-beta pathway and other pro-fibrotic mediators, it helps to maintain normal tissue architecture in organs like the heart and kidney. It has not been approved for clinical use.
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| Molecular Formula |
C22H34F3N5O11
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| Molecular Weight |
601.53
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| Related CAS # |
N-Acetyl-Ser-Asp-Lys-Pro acetate;N-Acetyl-Ser-Asp-Lys-Pro;127103-11-1
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| Appearance |
White to off-white solid powder
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: Please store this product in a sealed and protected environment, avoid exposure to moisture. |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
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| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.6624 mL | 8.3121 mL | 16.6243 mL | |
| 5 mM | 0.3325 mL | 1.6624 mL | 3.3249 mL | |
| 10 mM | 0.1662 mL | 0.8312 mL | 1.6624 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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