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| Targets |
The primary target of Asp-AMS is aspartyl-tRNA synthetase (AspRS), an enzyme essential for protein synthesis that catalyzes the attachment of aspartic acid to its cognate tRNA. Asp-AMS also acts as a potent competitive inhibitor of mitochondrial enzymes. The compound exhibits differential selectivity, showing stronger inhibitory effects on bacterial AspRS from organisms such as E. coli and Pseudomonas aeruginosa compared to human cytosolic AspRS. Additionally, Asp-AMS targets the mitochondrial isoform of AspRS with high affinity.
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| ln Vitro |
Compared to aspartate-AMP (10 nM), which is a 500-fold more effective inhibitor of mitochondrial enzymes, Asp-AMS is 35 times less competitive than human and bovine cytochrome-AspRSs (300 nM). With Ki in the nanomolar (nM) range, Asp-AMS is a potent inhibitor. The greatest inhibitory effect on mitochondrial enzymes was similarly observed with Asp-AMS. With Ki values in the nanomolar range, Asp-AMS is the most potent inhibitor and is more effective against bacterial AspRS (such as E. coli and Pseudomonas aeruginosa) than against human cytosolic AspRS [1].
Asp-AMS demonstrates potent in vitro inhibitory activity against aspartyl-tRNA synthetase. It is a 500-fold stronger competitive inhibitor of the mitochondrial enzyme than aspartol-AMP (10 nM). Against human and bovine cytosolic AspRS, Asp-AMS is a 35-fold weaker competitor (300 nM). The compound exhibits Ki values in the nanomolar range, establishing it as one of the most active inhibitors for mitochondrial AspRS. Asp-AMS shows greater potency against bacterial AspRS compared to the human cytosolic enzyme, indicating species selectivity. |
| ln Vivo |
In vivo activity data for Asp-AMS are currently limited, as the compound is primarily utilized in biochemical and cell-based assays rather than animal models. Based on its potent in vitro inhibition of aspartyl-tRNA synthetase and mitochondrial enzymes with nanomolar Ki values, Asp-AMS is anticipated to disrupt protein synthesis and mitochondrial function in living systems. However, comprehensive pharmacokinetic and pharmacodynamic studies in animal models have not been extensively reported. The compound remains a research tool for studying aminoacyl-tRNA synthetase biology and mitochondrial enzyme function rather than a therapeutic candidate with established in vivo efficacy.
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| Enzyme Assay |
The in vitro enzyme/receptor binding assay for Asp-AMS typically involves measuring its inhibitory activity against aspartyl-tRNA synthetase using enzymatic activity assays. The assay system includes purified AspRS enzyme, its natural substrate aspartic acid, ATP, and tRNA, with reaction progress monitored via ATP consumption or aminoacylation of tRNA. Asp-AMS is added at varying concentrations to determine IC50 or Ki values. Ki determination is performed using Lineweaver-Burk or Dixon plot analyses by measuring enzyme activity at different substrate and inhibitor concentrations. The assay buffer typically contains Tris-HCl, magnesium chloride, potassium chloride, and DTT at physiological pH. Reactions are incubated at 37degC and terminated by addition of trichloroacetic acid or SDS, followed by quantification of product formation.
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| Cell Assay |
The in vitro cell-based assay for Asp-AMS involves culturing relevant cell lines (e.g., mammalian or bacterial cells) and treating them with varying concentrations of the compound. Cells are typically seeded in multi-well plates and incubated for 24-72 hours in appropriate growth media at 37degC with 5% CO2. Following treatment, cell viability is assessed using standard assays such as MTT, CCK-8, or ATP-lite to determine IC50 values. Additionally, the compound's effect on protein synthesis can be evaluated by measuring incorporation of radiolabeled amino acids or by Western blot analysis of specific protein expression levels. Mitochondrial function can be assessed via oxygen consumption rate measurements or mitochondrial membrane potential assays using fluorescent dyes such as JC-1.
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| Animal Protocol |
In vivo animal studies for Asp-AMS have not been extensively documented in the literature. Based on the compound's mechanism as an aspartyl-tRNA synthetase inhibitor, potential animal studies would typically involve administration of the compound via intraperitoneal, intravenous, or oral routes in rodent models. Dosing would be determined based on preliminary pharmacokinetic data and solubility profiles. Common endpoints in such studies would include evaluation of enzyme inhibition in target tissues, assessment of protein synthesis inhibition, and monitoring of general toxicity parameters. However, as Asp-AMS is primarily a research reagent for biochemical studies, comprehensive in vivo animal efficacy and toxicity studies have not been widely reported.
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| ADME/Pharmacokinetics |
Pharmacokinetic properties of Asp-AMS have not been fully characterized in the literature. Based on its physicochemical properties, the compound has a molecular weight of 461.41 g/mol, a LogP of -6.5 indicating high hydrophilicity, and 6 hydrogen bond donors and 14 hydrogen bond acceptors. The compound shows good solubility in DMSO (100 mg/mL) and has been formulated for in vivo studies using 10% DMSO + 40% PEG300 + 5% Tween-80 + 45% saline. The high polarity (LogP -6.5) suggests limited oral bioavailability and potential challenges with membrane permeability. The compound is stable when stored as powder at -20degC for 3 years or at 4degC for 2 years, and in solution at -80degC for 6 months or -20degC for 1 month.
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| Toxicity/Toxicokinetics |
Toxicity data for Asp-AMS are not extensively documented in the available literature. As a research-use compound intended for in vitro biochemical and cell-based studies, comprehensive toxicological profiling in animal models has not been reported. Based on its mechanism as an aspartyl-tRNA synthetase inhibitor, potential toxicity would likely relate to disruption of protein synthesis and mitochondrial function in cells. The compound's high polarity (LogP -6.5) may limit cellular uptake and reduce systemic toxicity. Standard safety precautions should be followed when handling this compound, including the use of appropriate personal protective equipment. As with all research chemicals, proper waste disposal procedures should be observed and exposure should be minimized.
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| References | |
| Additional Infomation |
Asp-AMS (CAS#: 828288-98-8) is a research-grade compound with the molecular formula C14H1₉N₇O₉S and a molecular weight of 461.41. It is an analogue of aspartyl-adenylate that functions as both an aspartyl-tRNA synthetase inhibitor and a potent competitive inhibitor of mitochondrial enzymes. The compound exhibits Ki values in the nanomolar range and shows differential selectivity, with stronger effects on bacterial AspRS compared to human cytosolic AspRS. Asp-AMS has been cited in peer-reviewed literature including studies published in Biochimie. It is intended for research purposes only and is not approved for clinical use or human consumption. No clinical trials or regulatory approvals have been reported for this compound.
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| Molecular Formula |
C14H19N7O9S
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| Molecular Weight |
461.407160997391
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| Exact Mass |
461.096
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| CAS # |
828288-98-8
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| PubChem CID |
11190411
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| Appearance |
White to off-white solid powder
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| LogP |
-6.5
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| Hydrogen Bond Donor Count |
6
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| Hydrogen Bond Acceptor Count |
14
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| Rotatable Bond Count |
8
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| Heavy Atom Count |
31
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| Complexity |
781
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| Defined Atom Stereocenter Count |
5
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| SMILES |
O[C@@H]1[C@H](O)[C@@H](COS(=O)(=O)NC(=O)[C@@H](N)CC(=O)O)O[C@H]1N1C=NC2C(=NC=NC1=2)N
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| InChi Key |
KMRBRMHHDAUXAY-UFIIOMENSA-N
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| InChi Code |
InChI=1S/C14H19N7O9S/c15-5(1-7(22)23)13(26)20-31(27,28)29-2-6-9(24)10(25)14(30-6)21-4-19-8-11(16)17-3-18-12(8)21/h3-6,9-10,14,24-25H,1-2,15H2,(H,20,26)(H,22,23)(H2,16,17,18)/t5-,6+,9+,10+,14+/m0/s1
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| Chemical Name |
(3S)-3-amino-4-[[(2R,3S,4R,5R)-5-(6-aminopurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methoxysulfonylamino]-4-oxobutanoic acid
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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 : ~100 mg/mL (~216.73 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (5.42 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 (5.42 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 (5.42 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 | 2.1673 mL | 10.8363 mL | 21.6727 mL | |
| 5 mM | 0.4335 mL | 2.1673 mL | 4.3345 mL | |
| 10 mM | 0.2167 mL | 1.0836 mL | 2.1673 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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