| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
|
||
| 5mg | |||
| Other Sizes |
| Targets |
Sampatrilat targets two key enzymes: angiotensin-converting enzyme (ACE) and neutral endopeptidase (NEP). ACE is a zinc dipeptidyl carboxypeptidase with two extracellular domains (nACE and cACE). By inhibiting ACE, it prevents the formation of angiotensin II, a potent vasoconstrictor. By inhibiting NEP, it prevents the breakdown of natriuretic peptides, which promote vasodilation and sodium excretion. This combined action on both targets makes it a vasopeptidase inhibitor.
|
|---|---|
| ln Vitro |
Sampatrilat has demonstrated significant in vitro activity as an inhibitor of both ACE and NEP. Enzyme inhibition assays have been performed to evaluate its in vitro ACE domain selectivity, showing that it inhibits the C-domain of ACE with greater potency than the N-domain. The compound's Ki values for the C-domain and N-domain of ACE are 13.8 nM and 171.9 nM, respectively. This indicates a strong and selective inhibitory profile in cell-free systems.
|
| ln Vivo |
Sampatrilat (oral; 30 mg/kg; once daily; 5 weeks) increases survival and hemodynamics in CAL rats and decreases mortality (20% vs. 57% in untreated rats). It also enhances learning function calibration. This substance reduces CAL-induced increases in left ventricular end-diastolic pressure, heart weight, and left ventricular collagen content, but it does so without changing arterial blood pressure. It also suppresses tissue ACE and neutral endopeptidase (NEP) activities. ventricles [2].
Sampatrilat has shown in vivo efficacy in animal models of chronic heart failure. In rats with left coronary artery ligation (CAL), oral administration of Sampatrilat at 30 mg/kg once daily for 5 weeks increased survival rates and improved hemodynamic function. It significantly reduced mortality (20% vs. 57% in untreated rats). The compound also reduced left ventricular end-diastolic pressure, heart weight, and left ventricular collagen content without altering arterial blood pressure. Additionally, it suppressed tissue ACE and NEP activities. |
| Enzyme Assay |
The in vitro enzyme inhibition assays for Sampatrilat typically involve measuring its ability to inhibit the enzymatic activity of recombinant human ACE domains. The C-domain and N-domain of human somatic ACE are expressed in CHO cells. Enzyme activity is measured using a substrate such as Z-FHL (for the C-domain). The compound is preincubated with the enzyme before adding the substrate. The extent of inhibition is determined by measuring the decrease in product formation, allowing for the calculation of Ki values.
|
| Cell Assay |
While specific cell-based assay protocols for Sampatrilat are not detailed in the provided search results, the in vitro activity is primarily characterized through enzyme inhibition assays. The compound's effects on cellular processes related to ACE and NEP inhibition, such as angiotensin II production or natriuretic peptide degradation, can be studied in relevant cell lines (e.g., endothelial cells or cardiac myocytes) to confirm its mechanism of action. However, the core in vitro characterization relies on biochemical enzyme assays.
|
| Animal Protocol |
Animal/Disease Models: Left coronary artery ligation (CAL) and sham-operated rats [2]
Doses: 30 mg/kg Route of Administration: Oral Experimental Results:Prevented the increase in heart weight and myocardial collagen content in CAL rats. In vivo animal experiments have been conducted using a rat model of chronic heart failure induced by left coronary artery ligation (CAL). Sampatrilat was administered orally at a dose of 30 mg/kg once daily for 5 weeks. The study evaluated survival rates, hemodynamic function, and parameters of cardiac remodeling such as heart weight and myocardial collagen content. The results showed that Sampatrilat treatment prevented the increase in heart weight and myocardial collagen content in CAL rats. |
| ADME/Pharmacokinetics |
Sampatrilat (UK-81252) is an orally active compound. Its molecular weight is 584.68, and its molecular formula is C26H40N4O9S. For research purposes, the powder should be stored at -20°C for up to 3 years, and in solvent at -80°C for up to 1 year. It is shipped with blue ice or at ambient temperature. The compound is soluble in DMSO. For in vivo studies, a common formulation is 5% DMSO + 30% PEG300 + 5% Tween 80 + 60% saline.
|
| Toxicity/Toxicokinetics |
Sampatrilat is a research compound and its full toxicological profile is not detailed in the provided sources. In the in vivo rat model of chronic heart failure, the compound was tolerated at the tested dose of 30 mg/kg for 5 weeks, with no significant adverse effects on arterial blood pressure reported. However, as with any potent enzyme inhibitor, potential off-target effects and toxicity would need to be thoroughly evaluated in more comprehensive preclinical safety studies.
|
| References |
|
| Additional Infomation |
Sampatrilat is a potent, orally active vasopeptidase inhibitor that suppresses both ACE and NEP, also known as UK-81252. It is classified as a vasopeptidase inhibitor and has been studied for its potential in treating chronic heart failure and regulating blood pressure. Its mechanism involves dual inhibition of ACE and NEP, which may offer advantages over traditional ACE inhibitors alone. Sampatrilat is a research compound and has not been approved for clinical use.
|
| Molecular Formula |
C26H40N4O9S
|
|---|---|
| Molecular Weight |
584.685
|
| Exact Mass |
584.252
|
| CAS # |
129981-36-8
|
| PubChem CID |
6324648
|
| Appearance |
White to off-white solid powder
|
| Density |
1.343g/cm3
|
| Index of Refraction |
1.584
|
| LogP |
4.313
|
| Hydrogen Bond Donor Count |
7
|
| Hydrogen Bond Acceptor Count |
11
|
| Rotatable Bond Count |
17
|
| Heavy Atom Count |
40
|
| Complexity |
971
|
| Defined Atom Stereocenter Count |
3
|
| SMILES |
CS(=O)(=O)N[C@@H](CCCCN)C(=O)NC[C@H](CC1(CCCC1)C(=O)N[C@@H](CC2=CC=C(C=C2)O)C(=O)O)C(=O)O
|
| InChi Key |
LPUDGHQMOAHMMF-JBACZVJFSA-N
|
| InChi Code |
InChI=1S/C26H40N4O9S/c1-40(38,39)30-20(6-2-5-13-27)22(32)28-16-18(23(33)34)15-26(11-3-4-12-26)25(37)29-21(24(35)36)14-17-7-9-19(31)10-8-17/h7-10,18,20-21,30-31H,2-6,11-16,27H2,1H3,(H,28,32)(H,29,37)(H,33,34)(H,35,36)/t18-,20-,21-/m0/s1
|
| Chemical Name |
(2S)-2-[[[(2S)-6-amino-2-(methanesulfonamido)hexanoyl]amino]methyl]-3-[1-[[(1S)-1-carboxy-2-(4-hydroxyphenyl)ethyl]carbamoyl]cyclopentyl]propanoic acid
|
| Synonyms |
UK 81252; UK-81252; Sampatrilat
|
| HS Tariff Code |
2934.99.9001
|
| 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)
|
| Solubility (In Vitro) |
DMSO : ~100 mg/mL (~171.03 mM)
|
|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (4.28 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (4.28 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.5 mg/mL (4.28 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.7103 mL | 8.5515 mL | 17.1031 mL | |
| 5 mM | 0.3421 mL | 1.7103 mL | 3.4206 mL | |
| 10 mM | 0.1710 mL | 0.8552 mL | 1.7103 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.
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
