| Size | Price | Stock | Qty |
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| Targets |
Lenampicillin targets bacterial penicillin-binding proteins (PBPs), specifically the transpeptidase enzymes involved in bacterial cell wall synthesis. As a prodrug of ampicillin, Lenampicillin is converted to ampicillin after oral administration, and the released ampicillin exerts its antibacterial effect by inhibiting PBPs. This inhibition prevents the cross-linking of peptidoglycan chains in the bacterial cell wall, leading to cell wall instability and ultimately bacterial lysis and death. The compound is effective against a wide range of Gram-positive and Gram-negative bacteria, including Streptococcus pneumoniae, Staphylococcus aureus (non-penicillinase-producing), Escherichia coli, Haemophilus influenzae, and other ampicillin-sensitive organisms. Like other β-lactam antibiotics, Lenampicillin is bactericidal and time-dependent in its killing activity.
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| ln Vitro |
In vitro, Lenampicillin itself has limited antibacterial activity, as it is a prodrug that requires hydrolysis to release the active ampicillin. However, upon conversion to ampicillin, the compound exhibits potent antibacterial activity against a broad spectrum of bacteria. The in vitro activity of ampicillin (and thus Lenampicillin after hydrolysis) is characterized by minimum inhibitory concentration (MIC) values that vary depending on the bacterial species and the presence of β-lactamase enzymes. Ampicillin is highly active against many Gram-positive bacteria and some Gram-negative bacteria. The compound's activity is reduced in the presence of β-lactamase-producing bacteria, which can hydrolyze the β-lactam ring and inactivate the antibiotic. In vitro susceptibility testing is performed using standard broth dilution or agar diffusion methods according to Clinical and Laboratory Standards Institute (CLSI) guidelines.
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| ln Vivo |
Dogs treated orally with lenamcillin hydrochloride (KBT-1585; 0-1000 mg/kg) did not die, and vomiting was the source of the maximum dose observed in this acute toxicity trial [2]. In rats and dogs, lenamcillin hydrochloride, or LAPC, has been found to be a significant metabolite. When LAPC was administered to rats and dogs, the primary metabolite in peripheral plasma was 2,3-butanediol, while portal plasma had elevated acetoin levels. These findings suggest that whereas acetoin is converted to 2,3-butanediol in the liver, promoiety is mostly biotransformed to acetoin in intestinal tissue in LAPC [3].
In vivo, Lenampicillin demonstrates efficacy in animal models of bacterial infection. After oral administration, the prodrug is rapidly absorbed from the gastrointestinal tract and hydrolyzed to ampicillin, achieving higher and more consistent plasma concentrations compared to oral administration of ampicillin itself. This improved bioavailability results in better antibacterial efficacy in vivo. In murine models of systemic infection, Lenampicillin has been shown to protect against lethal doses of ampicillin-sensitive bacteria. The compound's efficacy is comparable to that of parenterally administered ampicillin, making it a viable oral alternative. In clinical studies, Lenampicillin has been shown to be effective in treating respiratory, urinary, and gastrointestinal tract infections. |
| Enzyme Assay |
The non-cellular assay for Lenampicillin involves measuring the hydrolysis of the prodrug to ampicillin in biological matrices, such as plasma or tissue homogenates. The compound is incubated with the biological matrix at 37°C, and samples are taken at various time points. The concentration of ampicillin released is quantified by high-performance liquid chromatography (HPLC) with UV detection or by liquid chromatography-mass spectrometry (LC-MS). The rate and extent of hydrolysis are determined, and the stability of the prodrug in different matrices is assessed. In addition, the antibacterial activity of the hydrolyzed product can be confirmed by bioassay, where the samples are tested for their ability to inhibit the growth of a susceptible indicator organism (such as Bacillus subtilis or Staphylococcus aureus). The potency of ampicillin after hydrolysis is compared to that of a standard ampicillin reference.
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| Cell Assay |
The cellular assay for Lenampicillin involves testing the antibacterial activity of the compound in cell culture models of infection. The compound is added to cultures of bacteria in the presence or absence of cells (such as macrophages or epithelial cells) that may affect the hydrolysis of the prodrug or the activity of the released antibiotic. After incubation, bacterial growth is measured by colony counting or by optical density. The MIC is determined for various bacterial strains. The compound's activity in the presence of serum or tissue components is also assessed to mimic the in vivo environment. Cytotoxicity of the prodrug and its active metabolite is evaluated in mammalian cell lines to ensure that the compound is not toxic to host cells at therapeutic concentrations.
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| Animal Protocol |
The in vivo animal studies for Lenampicillin typically use murine models of bacterial infection. Mice are infected with a lethal dose of an ampicillin-sensitive bacterial strain (such as Streptococcus pneumoniae or Escherichia coli) by intraperitoneal or intranasal administration. Lenampicillin is administered orally at various doses (typically 10-100 mg/kg) at defined time points after infection. The survival rate is monitored over a period of several days, and the protective effect of the compound is compared to that of vehicle-treated controls and positive controls (such as parenteral ampicillin). In addition to survival studies, the bacterial load in tissues (such as blood, lung, or spleen) is measured by plating serial dilutions on agar plates and counting colony-forming units (CFU). The pharmacokinetic profile of the prodrug and ampicillin is also assessed in parallel studies.
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| ADME/Pharmacokinetics |
Lenampicillin hydrochloride has a molecular weight of 497.95 g/mol and a molecular formula of C₂₁H₂₄ClN₃O₇S. The compound is an ester prodrug that is rapidly hydrolyzed to ampicillin after oral absorption. Its aqueous solubility is improved by the hydrochloride salt form, facilitating oral formulation. The compound is stable under dry storage conditions and should be stored in a cool, dry place. The pharmacokinetic properties of Lenampicillin are characterized by rapid absorption and extensive presystemic and systemic hydrolysis to ampicillin, resulting in high bioavailability of the active drug.
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| Toxicity/Toxicokinetics |
Lenampicillin hydrochloride is generally well-tolerated in clinical use, with a safety profile similar to that of other penicillins. The most common side effects are gastrointestinal disturbances, including diarrhea, nausea, and abdominal discomfort, which are associated with oral ampicillin therapy. Allergic reactions, including rash and anaphylaxis, can occur in penicillin-sensitive individuals. The prodrug formulation is designed to reduce gastrointestinal side effects by improving absorption and reducing the local concentration of ampicillin in the gut. As with other β-lactam antibiotics, hypersensitivity to penicillins is a contraindication. The compound is not recommended for use in patients with a history of penicillin allergy.
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| References | |
| Additional Infomation |
Valylcillin (TN) is a peptide.
Lenampicillin hydrochloride (KBT 1585) is an oral prodrug of ampicillin that was developed to improve the oral bioavailability of ampicillin and to reduce gastrointestinal side effects. It is used clinically in the treatment of respiratory, urinary, and gastrointestinal tract infections caused by ampicillin-sensitive bacteria. The prodrug approach has been successful in achieving higher and more consistent plasma concentrations of ampicillin, making it a convenient and effective oral alternative to parenteral ampicillin therapy. Lenampicillin is one of several ester prodrugs of ampicillin, including pivampicillin and bacampicillin, that have been developed to overcome the poor oral absorption of the parent drug. The compound continues to be used in clinical practice in some regions and remains a subject of research for its pharmacokinetic and clinical properties. |
| Molecular Formula |
C21H24CLN3O7S
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|---|---|
| Molecular Weight |
497.94
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| Exact Mass |
497.102
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| CAS # |
80734-02-7
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| PubChem CID |
6917773
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| Appearance |
White to off-white solid powder
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| Boiling Point |
717.4ºC at 760 mmHg
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| Flash Point |
387.7ºC
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| LogP |
1.86
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
9
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| Rotatable Bond Count |
7
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| Heavy Atom Count |
33
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| Complexity |
868
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| Defined Atom Stereocenter Count |
4
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| SMILES |
CC1=C(OC(=O)O1)COC(=O)[C@H]2C(S[C@H]3N2C(=O)[C@H]3NC(=O)[C@@H](C4=CC=CC=C4)N)(C)C.Cl
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| InChi Key |
FXXSETTYJSGMCR-GLCLSGQWSA-N
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| InChi Code |
InChI=1S/C21H23N3O7S.ClH/c1-10-12(31-20(28)30-10)9-29-19(27)15-21(2,3)32-18-14(17(26)24(15)18)23-16(25)13(22)11-7-5-4-6-8-11;/h4-8,13-15,18H,9,22H2,1-3H3,(H,23,25);1H/t13-,14-,15+,18-;/m1./s1
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| Chemical Name |
(5-methyl-2-oxo-1,3-dioxol-4-yl)methyl (2S,5R,6R)-6-[[(2R)-2-amino-2-phenylacetyl]amino]-3,3-dimethyl-7-oxo-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylate;hydrochloride
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| Synonyms |
Lenampicilline Hydrochloride; Takacillin; Lenampicillin Hydrochloride
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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 Note: Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture and light. |
| 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 (~200.82 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (5.02 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 (5.02 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 (5.02 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 | 2.0083 mL | 10.0414 mL | 20.0827 mL | |
| 5 mM | 0.4017 mL | 2.0083 mL | 4.0165 mL | |
| 10 mM | 0.2008 mL | 1.0041 mL | 2.0083 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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