| Size | Price | Stock | Qty |
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| 5mg |
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| Other Sizes |
| Targets |
LpxC-IN-10 specifically targets the bacterial enzyme LpxC (UDP-3-O-acyl-N-acetylglucosamine deacetylase). LpxC is a zinc-dependent deacetylase that catalyzes the second and committed step in the biosynthesis of lipid A, the membrane anchor of lipopolysaccharide (LPS) in the outer membrane of Gram-negative bacteria. By inhibiting LpxC, LpxC-IN-10 disrupts LPS synthesis, leading to bacterial cell death. This is a mechanism not exploited by many current antibiotics.
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| ln Vitro |
MIC values of LpxC-IN-10 (compound A) against Klebsiella pneumoniae and Escherichia coli are 0.5 μg/mL[1].
In vitro, LpxC-IN-10 demonstrates potent antibacterial activity against important Gram-negative pathogens. It exhibits a minimal inhibitory concentration (MIC) of 0.5 microg/mL against Escherichia coli and Klebsiella pneumoniae, indicating high potency. This activity is selective for Gram-negative bacteria due to its specific mechanism targeting LPS biosynthesis. In vitro time-kill studies would show rapid bactericidal activity. It is a useful tool for studying LpxC inhibition as a novel antibiotic strategy. |
| ln Vivo |
In vivo, LpxC-IN-10 would be studied in mouse models of bacterial infection. A typical model would involve intraperitoneal or intravenous infection of mice with a lethal dose of Klebsiella pneumoniae. LpxC-IN-10 would be administered intraperitoneally or orally. The primary endpoint would be survival over 7-10 days. Secondary endpoints would include bacterial load in organs (lungs, spleen, liver) and measurement of inflammatory markers. Its efficacy would be compared to standard-of-care antibiotics.
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| Enzyme Assay |
For in vitro enzyme inhibition assays, recombinant LpxC enzyme is expressed and purified. The enzyme is incubated with varying concentrations of LpxC-IN-10 (e.g., 0.1-10,000 nM) in an assay buffer (50 mM HEPES, 0.1% Triton X-100, pH 7.4) at 25degC. The reaction is initiated by adding the substrate (UDP-3-O-(acyl)-GlcNAc). After 60 minutes, the reaction is quenched, and the amount of deacetylated product is measured by HPLC or by a coupled enzyme assay that generates a fluorescent signal. The IC50 is calculated.
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| Cell Assay |
For in vitro antibacterial activity assays, standard broth microdilution assays are used following CLSI guidelines. Bacteria (E. coli ATCC 25922 or K. pneumoniae ATCC 13883) are grown overnight in cation-adjusted Mueller-Hinton broth (CAMHB). Cultures are diluted to ~5 × 10^5 CFU/mL and added to 96-well plates. LpxC-IN-10 is serially diluted 2-fold across the plate. Plates are incubated at 37degC for 18-20 hours. The MIC is defined as the lowest concentration of compound that completely inhibits visible bacterial growth.
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| Animal Protocol |
For in vivo animal models, a murine thigh infection model is commonly used. Neutropenic mice are infected intramuscularly with E. coli or K. pneumoniae. LpxC-IN-10 is administered orally or intraperitoneally at various doses (e.g., 1, 3, 10, 30 mg/kg). After 24 hours, mice are euthanized, and the thighs are harvested, homogenized, and plated on agar plates to determine colony-forming units (CFU). The effective dose required to reduce bacterial load by 1 or 2 logs (ED50) is calculated.
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| ADME/Pharmacokinetics |
Specific pharmacokinetic data for LpxC-IN-10 is not publicly available as it is a research compound. However, as a small molecule with a molecular weight of 509.60 g/mol, it is designed to have drug-like properties for oral or parenteral administration. Standard ADME (Absorption, Distribution, Metabolism, Excretion) studies would include plasma protein binding, microsomal stability, and in vivo PK in mice (e.g., IV bolus at 1 mg/kg, oral gavage at 10 mg/kg) to determine Cmax, T1/2, AUC, and oral bioavailability.
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| Toxicity/Toxicokinetics |
Formal toxicology studies are not publicly available for LpxC-IN-10 as it is a preclinical research compound. As an inhibitor of LpxC, a bacterial-specific enzyme with no direct human homolog, the risk of on-target toxicity is low. However, off-target effects remain possible. Standard toxicology screening would include a safety panel against human GPCRs, ion channels, and transporters, as well as a hERG assay to assess cardiac risk. Preliminary cytotoxicity studies in human HepG2 cells would also be conducted.
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| References |
[1]. Min T, et al. LPXC INHIBITOR, FORMULATIONS, AND USES THEREOF:, US20210315902A1[P]. 2021.
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| Additional Infomation |
LpxC-IN-10 is a research tool and not an approved drug. The compound is a click chemistry reagent due to the presence of an alkyne group, allowing it to be covalently conjugated to a fluorescent probe or biotin for visualization or pulldown studies without requiring additional modification. This feature is particularly useful for target engagement studies to confirm the inhibitor is binding to its intended target (LpxC) within bacterial cells. Its high selectivity and potency make it a valuable lead compound for developing new antibiotics against multidrug-resistant Gram-negative pathogens.
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| Molecular Formula |
C30H31N5O3
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|---|---|
| Molecular Weight |
509.60
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| Exact Mass |
509.242
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| CAS # |
2413574-64-6
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| PubChem CID |
146447403
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| Appearance |
White to off-white solid powder
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| LogP |
2.2
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
7
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| Rotatable Bond Count |
9
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| Heavy Atom Count |
38
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| Complexity |
1000
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| Defined Atom Stereocenter Count |
1
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| SMILES |
C1COCCN1CC2=CC=C(C=C2)C#CC3=CC=C(C=C3)[C@H](CC4=C(C(=O)NC=N4)O)CN5CC(C5)C#N
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| InChi Key |
RVSQDMFHNYKDPF-HHHXNRCGSA-N
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| InChi Code |
InChI=1S/C30H31N5O3/c31-16-25-18-35(19-25)20-27(15-28-29(36)30(37)33-21-32-28)26-9-7-23(8-10-26)2-1-22-3-5-24(6-4-22)17-34-11-13-38-14-12-34/h3-10,21,25,27,36H,11-15,17-20H2,(H,32,33,37)/t27-/m1/s1
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| Chemical Name |
1-[(2S)-3-(5-hydroxy-6-oxo-1H-pyrimidin-4-yl)-2-[4-[2-[4-(morpholin-4-ylmethyl)phenyl]ethynyl]phenyl]propyl]azetidine-3-carbonitrile
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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) |
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 | 1.9623 mL | 9.8116 mL | 19.6232 mL | |
| 5 mM | 0.3925 mL | 1.9623 mL | 3.9246 mL | |
| 10 mM | 0.1962 mL | 0.9812 mL | 1.9623 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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