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| Targets |
The primary target of Leu-AMS is leucyl tRNA synthetase (LeuRS), an enzyme that catalyzes the attachment of leucine to its cognate tRNA during protein synthesis. As a sulfamoyladenosine analog, Leu-AMS mimics the aminoacyl-adenylate intermediate of the aminoacylation reaction, allowing it to bind tightly to the active site of the enzyme. By inhibiting leucyl tRNA synthetase, Leu-AMS disrupts protein synthesis, leading to reduced cell proliferation and, in the case of bacteria, inhibition of growth. The compound's selectivity for the bacterial or eukaryotic enzyme determines its potential as an antibiotic or anticancer agent.
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| ln Vitro |
Leu-AMS was reported to be a strong inhibitor of leucyl-tRNA synthetase (LRS) with an IC50 value of 22.34 nM. Leu-AMS is extremely cytotoxic to both cancer cells and normal cells. Leu-AMS does not impact S6 kinase (S6K) phosphorylation at all. Leu-AMS decreases the catalytic activity of LRS but does not impact leucine-induced mTORC1 activation [1].
In vitro, Leu-AMS is a potent inhibitor of leucyl tRNA synthetase, binding tightly to the active site of the enzyme and preventing the aminoacylation of tRNA. The compound's inhibitory activity is concentration-dependent, with effects observed at nanomolar concentrations. Leu-AMS is used in research to study the role of leucyl tRNA synthetase in protein synthesis and to investigate the potential of aminoacyl-tRNA synthetase inhibitors as therapeutic agents. Its activity can be assessed using in vitro enzyme assays with recombinant leucyl tRNA synthetase. |
| ln Vivo |
In vivo, Leu-AMS has potential applications in studying bacterial infections and cancer. As an inhibitor of leucyl tRNA synthetase, the compound may be effective against bacteria that are dependent on protein synthesis for growth. It may also have anticancer activity by inhibiting protein synthesis in rapidly dividing cancer cells. However, in vivo studies are limited, and further research is needed to evaluate its efficacy, pharmacokinetics, and safety in animal models.
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| Enzyme Assay |
The in vitro enzyme inhibition activity of Leu-AMS can be assessed using cell-free assays with recombinant leucyl tRNA synthetase. A typical protocol involves incubating the enzyme with ATP, leucine, tRNA, and Leu-AMS at various concentrations in a reaction buffer. The reaction is carried out at 37degC for a specified period, and the amount of aminoacylated tRNA is measured using a radioactive or fluorescent assay. The IC50 value is determined by plotting the percentage of enzyme activity remaining against the compound concentration. The binding affinity of Leu-AMS to the enzyme can be assessed using surface plasmon resonance (SPR) or isothermal titration calorimetry (ITC).
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| Cell Assay |
For in vitro cellular experiments, cells (e.g., bacterial cells, cancer cell lines) are cultured in appropriate media and treated with Leu-AMS at various concentrations (typically 0.1-100 uM). For antibacterial studies, bacterial cultures are grown to logarithmic phase and treated with the compound, and growth inhibition is measured by optical density (OD600) or by plating serial dilutions and counting colony-forming units. For anticancer studies, cell viability is measured after 24-72 hours of treatment using MTT or CCK-8 assays. The duration of treatment varies depending on the experimental design.
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| Animal Protocol |
In vivo animal experiments with Leu-AMS would typically involve administration via intraperitoneal or intravenous injection in mouse models of bacterial infection or cancer. A common dosing regimen would be based on pharmacokinetic studies to determine the optimal dose and route of administration. For antibacterial studies, animals are infected with pathogenic bacteria, and Leu-AMS is administered either prophylactically or therapeutically. Bacterial load in blood and tissues is measured at various time points by plating serial dilutions. For anticancer studies, tumor-bearing mice are treated with the compound, and tumor growth is monitored by caliper measurements.
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| ADME/Pharmacokinetics |
Leu-AMS is a sulfamoyladenosine analog with a molecular weight similar to that of related compounds (approximately 500 g/mol). As a small molecule inhibitor, its pharmacokinetic properties would need to be characterized in preclinical studies, including absorption, distribution, metabolism, and excretion profiles. The compound is typically soluble in DMSO and should be stored at -20degC. Its half-life, oral bioavailability, and tissue distribution would be determined through pharmacokinetic studies.
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| Toxicity/Toxicokinetics |
The toxicity profile of Leu-AMS has not been extensively characterized. As an inhibitor of leucyl tRNA synthetase, which is essential for protein synthesis, the compound may have potential toxicity to rapidly dividing cells. However, its selectivity for the bacterial or eukaryotic enzyme would determine its safety profile. In vitro cytotoxicity studies would be needed to assess its effects on mammalian cell lines. In vivo toxicity studies in animal models would also be required to determine its safety profile. The compound should be handled with standard laboratory precautions and is intended for research use only.
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| References | |
| Additional Infomation |
Leu-AMS (CAS 288591-93-5) is a potent inhibitor of leucyl tRNA synthetase (LeuRS). As a sulfamoyladenosine analog, it mimics the aminoacyl-adenylate intermediate of the aminoacylation reaction, allowing it to bind tightly to the active site of the enzyme. By inhibiting leucyl tRNA synthetase, Leu-AMS disrupts protein synthesis, leading to reduced cell proliferation. The compound has potential applications in studying protein synthesis, bacterial infections, and cancer. Leu-AMS is available as a research compound and is not approved for clinical use.
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| Molecular Formula |
C16H25N7O7S
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|---|---|
| Molecular Weight |
459.47740149498
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| Exact Mass |
459.153
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| CAS # |
288591-93-5
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| Related CAS # |
Leu-AMS R enantiomer
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| PubChem CID |
5288690
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| Appearance |
White to off-white solid powder
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| LogP |
-2
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| Hydrogen Bond Donor Count |
5
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| Hydrogen Bond Acceptor Count |
12
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| Rotatable Bond Count |
8
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| Heavy Atom Count |
31
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| Complexity |
736
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| Defined Atom Stereocenter Count |
5
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| SMILES |
S(NC([C@H](CC(C)C)N)=O)(=O)(=O)OC[C@@H]1[C@H]([C@H]([C@H](N2C=NC3C(N)=NC=NC2=3)O1)O)O
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| InChi Key |
XFEDFDTWJLGMBO-LEJQEAHTSA-N
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| InChi Code |
InChI=1S/C16H25N7O7S/c1-7(2)3-8(17)15(26)22-31(27,28)29-4-9-11(24)12(25)16(30-9)23-6-21-10-13(18)19-5-20-14(10)23/h5-9,11-12,16,24-25H,3-4,17H2,1-2H3,(H,22,26)(H2,18,19,20)/t8-,9+,11+,12+,16+/m0/s1
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| Chemical Name |
[(2R,3S,4R,5R)-5-(6-aminopurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methyl N-[(2S)-2-amino-4-methylpentanoyl]sulfamate
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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 |
| 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) |
DMSO : ≥ 49.17 mg/mL (~107.01 mM)
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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 | 2.1764 mL | 10.8819 mL | 21.7637 mL | |
| 5 mM | 0.4353 mL | 2.1764 mL | 4.3527 mL | |
| 10 mM | 0.2176 mL | 1.0882 mL | 2.1764 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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