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| Targets |
(3R,4R)-A2-32-01 primarily targets Staphylococcus aureus caseinolytic protease (SaClpP), a key bacterial protease involved in protein quality control and virulence regulation. SaClpP is essential for bacterial pathogenesis and stress responses. By inhibiting SaClpP, the compound disrupts bacterial proteostasis and reduces virulence factor production. The specific (R,R) configuration at the chiral centers is important for its inhibitory activity. This anti-virulence approach aims to disarm pathogens without exerting selective pressure for antibiotic resistance.
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| ln Vitro |
In vitro, (3R,4R)-A2-32-01 functions as a specific caseinolytic protease (ClpP) inhibitor with an EC50 of 4.5 μM. The compound's activity is dependent on its (R,R) stereochemistry. It inhibits SaClpP activity in biochemical assays, demonstrating its potential as an anti-virulence agent. The compound shows specificity for bacterial ClpP without significant off-target effects. Its mechanism involves binding to the protease active site and preventing substrate processing.
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| ln Vivo |
In vivo activity of (3R,4R)-A2-32-01 has been demonstrated in animal models of Staphylococcus aureus infection. As an anti-virulence agent, the compound reduces bacterial pathogenicity without killing the bacteria directly. This approach minimizes the selection pressure for antibiotic resistance. The compound's efficacy is evaluated by measuring bacterial loads, virulence factor production, and host survival in infected animals. Specific in vivo data for this enantiomer is limited, but it shows promise as a novel therapeutic strategy.
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| Enzyme Assay |
The cell-free enzyme assay for (3R,4R)-A2-32-01 involves measuring its inhibitory activity against purified SaClpP protease. The assay typically uses fluorogenic peptide substrates that are cleaved by active ClpP. Inhibition is assessed by incubating the enzyme with varying concentrations of the compound (ranging from nM to μM) and measuring residual protease activity. The EC50 value of 4.5 μM is determined from dose-response curves. Selectivity is evaluated by testing the compound against other proteases to confirm specificity for SaClpP.
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| Cell Assay |
For in vitro cellular assays, (3R,4R)-A2-32-01 is typically dissolved in DMSO and diluted in bacterial culture medium. Staphylococcus aureus cultures are treated with various concentrations of the compound for defined periods. Bacterial growth is monitored to confirm that the compound does not kill bacteria directly but inhibits virulence. Virulence factor production (e.g., toxins, enzymes) is measured using biochemical assays or qPCR. The anti-virulence effect is evaluated by comparing virulence factor expression between treated and untreated cultures.
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| Animal Protocol |
In vivo animal studies for (3R,4R)-A2-32-01 are conducted in mouse models of Staphylococcus aureus infection. The compound is administered via various routes including intraperitoneal or oral administration. Bacterial loads in tissues (e.g., blood, spleen, kidneys) are measured by colony counting. Virulence factor production and host inflammatory responses are assessed using ELISA and histopathology. Survival studies evaluate the protective effect of the compound against lethal infection. Efficacy is compared to untreated controls and standard antibiotic treatments.
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| ADME/Pharmacokinetics |
Pharmacokinetic properties of (3R,4R)-A2-32-01 include a molecular weight of 301.42 g/mol and molecular formula C19H27NO2. The compound has a purity of 98% and is typically stored sealed in dry conditions at -20°C. As a small molecule inhibitor, it is expected to have moderate oral bioavailability and tissue penetration. Detailed ADME parameters such as half-life, Cmax, and AUC are not extensively reported in the available literature. Standard formulation vehicles such as DMSO, PEG300, and saline can be used for in vivo administration.
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| Toxicity/Toxicokinetics |
The toxicity profile of (3R,4R)-A2-32-01 has not been extensively characterized in published literature. As an anti-virulence agent that targets bacterial proteases, the compound is expected to have low mammalian toxicity due to the absence of the target in human cells. Standard preclinical safety studies would include acute and sub-chronic toxicity assessments in rodent models. The compound is intended for research use only and not for therapeutic applications in humans. Standard safety precautions should be followed when handling this compound.
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| References | |
| Additional Infomation |
(3R,4R)-A2-32-01 is the (R,R)-enantiomer of A2-32-01 and a specific inhibitor of Staphylococcus aureus caseinolytic protease (SaClpP) with an EC50 of 4.5 μM. It is a novel anti-virulence drug that targets bacterial proteases to reduce pathogenicity without directly killing bacteria. This approach aims to minimize antibiotic resistance selection pressure. The compound is a research tool for studying bacterial virulence and developing alternative therapeutic strategies for bacterial infections. (3R,4R)-A2-32-01 has not entered clinical trials and is strictly for research purposes.
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| Molecular Formula |
C19H27NO2
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|---|---|
| Molecular Weight |
301.423185586929
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| Exact Mass |
301.204
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| CAS # |
1359752-95-6
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| Related CAS # |
(3S,4S)-A2-32-01
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| PubChem CID |
57403969
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| Appearance |
Colorless to light yellow liquid
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| LogP |
5.3
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| Hydrogen Bond Donor Count |
0
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| Hydrogen Bond Acceptor Count |
3
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| Rotatable Bond Count |
11
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| Heavy Atom Count |
22
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| Complexity |
342
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| Defined Atom Stereocenter Count |
2
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| SMILES |
C=CCCCCCCC[C@@H]1[C@H](OC1=O)CCC2=CN=CC=C2
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| InChi Key |
WBHVHPLFRGISDD-QZTJIDSGSA-N
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| InChi Code |
InChI=1S/C19H27NO2/c1-2-3-4-5-6-7-8-11-17-18(22-19(17)21)13-12-16-10-9-14-20-15-16/h2,9-10,14-15,17-18H,1,3-8,11-13H2/t17-,18-/m1/s1
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| Chemical Name |
(3R,4R)-3-non-8-enyl-4-(2-pyridin-3-ylethyl)oxetan-2-one
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| Synonyms |
(3R,4R)A23201 (3R,4R) A2 32 01
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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 : ~200 mg/mL (~663.53 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 5 mg/mL (16.59 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 50.0 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: ≥ 5 mg/mL (16.59 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 50.0 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: ≥ 5 mg/mL (16.59 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 | 3.3176 mL | 16.5881 mL | 33.1763 mL | |
| 5 mM | 0.6635 mL | 3.3176 mL | 6.6353 mL | |
| 10 mM | 0.3318 mL | 1.6588 mL | 3.3176 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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