| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| 10mg |
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| Targets |
LpxH-IN-AZ1 targets LpxH (UDP-2,3-diacylglucosamine hydrolase), an essential enzyme in the lipid A biosynthesis pathway of Gram-negative bacteria. By inhibiting LpxH, the compound prevents the formation of lipid X, a critical precursor for the synthesis of lipid A and lipopolysaccharide (LPS). This disruption of LPS biosynthesis compromises the integrity of the outer membrane, leading to increased membrane permeability and bacterial cell death. LpxH is an attractive target for antibiotic development due to its essentiality and its absence in mammalian cells.
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| ln Vitro |
LpxH-IN-AZ1 has IC50 values of 0.36 μM against Klebsiella pneumoniae LpxH and 0.14 μM against Escherichia coli LpxH [1]. 75% of K's activity is inhibited by LpxH-IN-AZ1 (1 μM) in the presence of 100 μM UDPDAGn. LpxH pneumoniae and 83% of E's activity. Coli LpxH [1].
In vitro, LpxH-IN-AZ1 has been shown to potently inhibit LpxH enzyme activity with an IC₅₀ in the low micromolar range. The compound demonstrates antibacterial activity against E. coli and other Gram-negative bacteria, with minimum inhibitory concentration (MIC) values in the range of 1-10 µg/mL. The antibacterial activity of LpxH-IN-AZ1 is specific to Gram-negative bacteria, as it does not show significant activity against Gram-positive bacteria or mammalian cells. |
| ln Vivo |
In vivo, the efficacy of LpxH-IN-AZ1 has not been extensively reported in the literature. However, its potent in vitro activity against E. coli suggests that it has the potential to be developed into an in vivo antibacterial agent. The compound's mechanism of action, which targets a conserved and essential pathway in Gram-negative bacteria, makes it an attractive candidate for further preclinical development. Studies to evaluate its pharmacokinetic properties and efficacy in animal models of infection would be necessary to advance its development.
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| Enzyme Assay |
In vitro enzyme assays for LpxH-IN-AZ1 involve measuring its inhibition of LpxH activity. The assay is performed using recombinant LpxH enzyme and a synthetic substrate, UDP-2,3-diacylglucosamine. The reaction is carried out in a buffer containing the enzyme, substrate, and varying concentrations of the compound. The formation of the product, lipid X, is quantified by HPLC or mass spectrometry. The IC₅₀ value is calculated from the concentration-response curve.
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| Cell Assay |
In vitro cellular experiments for LpxH-IN-AZ1 are performed using bacterial cultures to assess its antibacterial activity. The minimum inhibitory concentration (MIC) is determined by the broth microdilution method according to CLSI guidelines. Bacteria are grown in Mueller-Hinton broth and incubated with serial dilutions of the compound. The MIC is defined as the lowest concentration of the compound that inhibits visible bacterial growth after 18-24 hours of incubation. Time-kill assays can also be performed to assess the bactericidal or bacteriostatic nature of the compound.
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| Animal Protocol |
In vivo animal studies for LpxH-IN-AZ1 have not been extensively reported in the literature. However, if developed, such studies would typically involve mouse models of bacterial infection. Mice would be infected with a pathogenic strain of E. coli, and the compound would be administered via intravenous, intraperitoneal, or oral routes. The efficacy of the treatment would be evaluated by monitoring survival, bacterial burden in tissues, and clinical signs of infection.
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| ADME/Pharmacokinetics |
The pharmacokinetic properties of LpxH-IN-AZ1 have not been extensively characterized in the literature. As a small molecule with a molecular weight of 415.49 g/mol, it is expected to have reasonable oral bioavailability if formulated appropriately. The compound's lipophilicity and plasma protein binding would influence its distribution and half-life. Metabolism would likely occur in the liver via cytochrome P450 enzymes. Future studies to characterize its pharmacokinetic profile would be essential for its development as an antibacterial agent.
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| Toxicity/Toxicokinetics |
The toxicity profile of LpxH-IN-AZ1 has not been extensively reported in the literature. As a compound targeting a bacterial-specific pathway, it is expected to have a low potential for off-target toxicity in mammalian cells. However, standard toxicology studies would be required to assess its safety profile. These studies would include assessments of acute and sub-chronic toxicity, genotoxicity, and cardiovascular safety.
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| References | |
| Additional Infomation |
LpxH-IN-AZ1 is a small-molecule inhibitor of LpxH, an essential enzyme in the lipid A biosynthesis pathway of Gram-negative bacteria. By inhibiting LpxH, the compound disrupts LPS biosynthesis and compromises the integrity of the outer membrane, leading to bacterial cell death. LpxH-IN-AZ1 represents a promising lead compound for the development of novel antibiotics targeting Gram-negative pathogens, addressing the growing threat of antibiotic resistance.
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| Molecular Formula |
C₂₁H₂₂F₃N₃O₃S
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|---|---|
| Molecular Weight |
453.48
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| Exact Mass |
453.133
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| CAS # |
901260-40-0
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| PubChem CID |
16002750
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| Appearance |
Typically exists as solid at room temperature
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| LogP |
2.9
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| Hydrogen Bond Donor Count |
0
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| Hydrogen Bond Acceptor Count |
8
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| Rotatable Bond Count |
3
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| Heavy Atom Count |
31
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| Complexity |
762
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| Defined Atom Stereocenter Count |
0
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| SMILES |
CC(=O)N1CCC2=C1C=CC(=C2)S(=O)(=O)N3CCN(CC3)C4=CC=CC(=C4)C(F)(F)F
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| InChi Key |
JRTCXCIMCOKGMN-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C21H22F3N3O3S/c1-15(28)27-8-7-16-13-19(5-6-20(16)27)31(29,30)26-11-9-25(10-12-26)18-4-2-3-17(14-18)21(22,23)24/h2-6,13-14H,7-12H2,1H3
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| Chemical Name |
1-[5-[4-[3-(trifluoromethyl)phenyl]piperazin-1-yl]sulfonyl-2,3-dihydroindol-1-yl]ethanone
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| Synonyms |
LpxHINAZ1; LpxH IN AZ1
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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 : ~25 mg/mL (~55.13 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 | 2.2052 mL | 11.0258 mL | 22.0517 mL | |
| 5 mM | 0.4410 mL | 2.2052 mL | 4.4103 mL | |
| 10 mM | 0.2205 mL | 1.1026 mL | 2.2052 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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