| Size | Price | |
|---|---|---|
| 500mg | ||
| 1g | ||
| Other Sizes |
| Targets |
Protease
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|---|---|
| ln Vitro |
Leupeptin Ac is a dipeptide. L-Leucinamide, N-acetyl-L-leucyl-N-[4-[(aminoiminomethyl)amino]-1-formylbutyl]- is a natural product found in Streptomyces roseus and Xenorhabdus bovienii with data available.
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| Enzyme Assay |
The unprecedented coronavirus SARS-CoV-2 outbreak at Wuhan, China, caused acute respiratory infection to humans. There is no precise vaccine/therapeutic agents available to combat the COVID-19 disease. Some repurposed drugs are saving the life of diseased, but the complete cure is relatively less. Several drug targets have been reported to inhibit the SARS-CoV-2 virus infection, in that TMPRSS2 (transmembrane protease serine 2) is one of the potential targets; inhibiting this protease stops the virus entry into the host human cell. Camostat mesylate, nafamostat, and leupeptin are the drugs, in which the first two drugs are being used for COVID-19 and leupeptin also tested. To consider these drugs as the repurposed drug for COVID-19, it is essential to understand their binding affinity and stability with TMPRSS2. In the present study, we performed the molecular docking and molecular dynamics (MD) simulation of these molecules with the TMPRSS2. The docking study reveals that leupeptin molecule strongly binds with TMPRSS2 protein than the other two drug molecules. The RMSD and RMSF values of MD simulation confirm that leupeptin and the amino acids of TMPRSS2 are very stable than the other two molecules. Furthermore, leupeptin forms interactions with the key amino acids of TMPRSS2 and the same have been maintained during the MD simulations. This structural and dynamical information is useful to evaluate these drugs to be used as repurposed drugs, however, the strong binding profile of leupeptin with TMPRSS2, suggests, it may be considered as a repurposed drug for COVID-19 disease after clinical trial.[3]
|
| References |
[1]. Leupeptins, new protease inhibitors from Actinomycetes. J Antibiot (Tokyo). 1969 Jun;22(6):283-6.
[2]. The structure and activity of leupeptins and related analogs. J Antibiot (Tokyo). 1971 Jun;24(6):402-4. [2]. Strong Binding of Leupeptin with TMPRSS2 Protease May Be an Alternative to Camostat and Nafamostat for SARS-CoV-2 Repurposed Drug: Evaluation from Molecular Docking and Molecular Dynamics Simulations. Appl Biochem Biotechnol. 2021 Jan 29;193(6):1909–1923. |
| Additional Infomation |
Leupeptin is a tripeptide composed of N-acetylleucyl, leucyl and argininal residues joined in sequenceby peptide linkages. It is an inhibitor of the calpains, a family of calcium-activated proteases which promote cell death. It has a role as a serine protease inhibitor, a bacterial metabolite, a cathepsin B inhibitor, a calpain inhibitor and an EC 3.4.21.4 (trypsin) inhibitor. It is a tripeptide and an aldehyde. It is a conjugate base of a leupeptin(1+).
Leupeptin has been reported in Streptomyces lavendulae, Streptomyces exfoliatus, and other organisms with data available. To address the urgent need of drugs to treat the COVID-19 pandemic disease, repurposing drugs is one of the best solutions comparing with the other techniques like vaccine development and new plasma transfusion. In the line of drug searching process, we have undertaken camostat, nafamostat, and leupeptin drug molecules to inhibit the TMPRSS2 serine 2 protease, which is the activator of SARS-CoV-2 for the fusion of the virus enter into the host human cell. The molecular docking study reveals that these three drug molecules form interactions and has binding affinity towards TMPRSS2. However, the leupeptin forms strong interactions with the key amino acids Ser186, His41, and Asp180 of catalytic triad present in the active site of TMPRSS2 as the other two molecules lacking Ser186 and His41 interactions, whereas in the molecular dynamics simulations of these three complexes, leupeptin is highly stable (RMSD & RMSF) and this molecule also forms stable interactions with the key amino acids Ser186, His41, and Asp186 of TMPRSS2 during the 100-ns MD simulations. On comparing the binding-free energy of all the three molecules, notably, leupeptin has high binding affinity towards TMPRSS2. From the above static and dynamic studies, it is confirmed that leupeptin is very stable and it could strongly inhibit the TRMPRSS2 serine 2 protease and this leads to stop the fusion of SARS-CoV-2 virus onto the host human cell, hence it is considered as a repurposed drug after clinical studies.[3] |
| Molecular Formula |
C20H38N6O4
|
|---|---|
| Molecular Weight |
426.55
|
| Exact Mass |
426.295
|
| Elemental Analysis |
C, 56.32; H, 8.98; N, 19.70; O, 15.00
|
| CAS # |
24365-47-7
|
| Related CAS # |
Leupeptin hemisulfate;103476-89-7;Leupeptin;55123-66-5; Leupeptin;55123-66-5;Leupeptin Ac-LL;24365-47-7; Leupeptin hemisulfate;103476-89-7; 39740-82-4 (HCl); 1082207-96-2 (hemisulfate hydrate)
|
| PubChem CID |
72429
|
| Appearance |
Typically exists as solid at room temperature
|
| Density |
1.21g/cm3
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| Index of Refraction |
1.557
|
| LogP |
2.378
|
| Hydrogen Bond Donor Count |
5
|
| Hydrogen Bond Acceptor Count |
5
|
| Rotatable Bond Count |
14
|
| Heavy Atom Count |
30
|
| Complexity |
602
|
| Defined Atom Stereocenter Count |
3
|
| SMILES |
N/C(=N/CCCC(NC([C@@H](NC([C@@H](NC(=O)C)CC(C)C)=O)CC(C)C)=O)C=O)/N
|
| InChi Key |
GDBQQVLCIARPGH-BSOSBYQFSA-N
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| InChi Code |
InChI=1S/C20H38N6O4/c1-12(2)9-16(24-14(5)28)19(30)26-17(10-13(3)4)18(29)25-15(11-27)7-6-8-23-20(21)22/h11-13,15-17H,6-10H2,1-5H3,(H,24,28)(H,25,29)(H,26,30)(H4,21,22,23)/t15?,16-,17-/m0/s1
|
| Chemical Name |
(2S)-2-acetamido-N-[(2S)-1-[[5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]-4-methylpentanamide
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| Synonyms |
Leupeptin Ac; 24365-47-7; Leupeptin Ac-LL; C01591; (2S)-2-acetamido-N-[(2S)-1-[[5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]-4-methylpentanamide; L-Leucinamide, N-acetyl-L-leucyl-N-[4-[(aminoiminomethyl)amino]-1-formylbutyl]-; AC1NR4EG; SCHEMBL4669504;
|
| 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 |
| 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) |
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 | 2.3444 mL | 11.7220 mL | 23.4439 mL | |
| 5 mM | 0.4689 mL | 2.3444 mL | 4.6888 mL | |
| 10 mM | 0.2344 mL | 1.1722 mL | 2.3444 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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