| Size | Price | Stock | Qty |
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| 5mg |
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| 50mg |
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Purity: ≥98%
Lefamulin (formerly also known as BC-3781; Xenleta) is a semi-synthetic, oral pleuromutilin antibiotic approved to treat adults with community-acquired bacterial pneumonia. It potently inhibits the synthesis of bacterial protein, which is required for bacteria to grow. Lefamulin acts by binding to the peptidyl transferase center, or PTC, on the bacterial ribosome in such a way that it interferes with the interaction of protein production at two key sites known as the 'A' site and the 'P' site, resulting in the inhibition of bacterial proteins and the cessation of bacterial growth. Lefamulin's binding occurs with high affinity, high specificity and at molecular sites that are different than other antibiotic classes. Lefamulin exhibited MIC50 and MIC90 values of 0.12 and 0.25 μg/ml, respectively, against the entire collection (n = 822). Similar results were obtained for lefamulin against each of the most common serotypes as well as against multidrug-resistant isolates and strains that are nonsusceptible to ceftriaxone or erythromycin. Lefamulin may be useful for the treatment of community-acquired respiratory tract infections.
| Targets |
Bacterial ribosome (peptidyl transferase center, PTC) [2]
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|---|---|
| ln Vitro |
Lefamulin (0–1 mg/L) inhibits the growth of N. gonorrhoeae, M. genitalium, and C. trachomatis[2].
With MIC values of less than 0.008 μg/mL, lefamulin exhibits strong activity against every strain of M. pneumoniae[3]. Lefamulin demonstrated potent in vitro activity against Chlamydia trachomatis (MIC₅₀/₉₀: 0.02/0.04 mg/L; range: 0.01–0.04 mg/L; n=15 serovars), including ocular, urogenital, and lymphogranuloma venereum strains. [2] Lefamulin showed activity against Mycoplasma genitalium, including multidrug-resistant strains (MIC range: 0.002–0.063 mg/L; n=6), and was more active than azithromycin, erythromycin, doxycycline, moxifloxacin, and ciprofloxacin against these strains. [2] Lefamulin exhibited activity against Neisseria gonorrhoeae (MIC₅₀/₉₀: 0.12/0.5 mg/L; n=24), comparable to azithromycin and more active than tetracycline. Activity was unchanged regardless of resistance to fluoroquinolones, tetracyclines, or penicillins. [2] Lefamulin accumulated intracellularly in murine macrophages and showed good tissue penetration, including into epithelial lining fluid. [2] |
| ln Vivo |
Lefamulin (10–140 mg/kg, s.c.) reduces inflammation in a mouse model of lung neutrophilia caused by lipopolysaccharide (LPS)[4].
In mice with lung infections caused by S. pneumoniae or S. aureus, lefamulin (1.25-160 mg/kg, s.c.) exhibits antibacterial activity[5]. In a lipopolysaccharide (LPS)-induced lung neutrophilia mouse model, a single subcutaneous (SC) dose of lefamulin (10, 30, 100 mg/kg) administered 30 minutes before intranasal LPS challenge resulted in a dose-dependent reduction in total cell and neutrophil counts in bronchoalveolar lavage fluid (BALF) at 4 hours post-challenge. The reduction was comparable to or more potent than SC azithromycin (10, 30, 100 mg/kg) and intraperitoneal dexamethasone (1 mg/kg). [4] Single SC doses of lefamulin (10, 30, 100 mg/kg) significantly and dose-dependently reduced LPS-induced levels of pro-inflammatory cytokines (TNF-α, IL-6, IL-1β, GM-CSF), chemokines (CXCL-1, CXCL-2, CCL-2), and MMP-9 in mouse lung tissue homogenates. The effects were comparable to or more potent than dexamethasone (1 mg/kg IP) or azithromycin (10, 30, 100 mg/kg SC). [4] |
| Cell Assay |
Cell Line: C. trachomatis, N. gonorrhoeae, and M. genitalium
Concentration: 0-1 mg/L Incubation Time: Result: MIC50s of 0.02 mg/L, 0.063 mg/L, and 0.12 mg/L, respectively, were used to inhibit bacterial activity. MIC determination for C. trachomatis was performed on monolayers of McCoy or HeLa 229 cells infected with C. trachomatis (10²–10³ IFU per 3×10⁵ cells) on glass coverslips. Drug concentrations ranged from 2.56 to 0.0003 mg/L. After incubation at 35°C (5% CO₂) for 48–72 h, cells were fixed in methanol, and inclusions were stained with an alcoholic iodine solution. MIC was defined as the lowest concentration with no inclusions observed. [2] Susceptibility testing of M. genitalium was performed using Vero cell culture and a quantitative real-time PCR method. [2] Susceptibility testing of N. gonorrhoeae was performed by agar dilution technique as per CLSI guidelines. [2] |
| Animal Protocol |
Animal Model: LPS-induced lung neutrophilia mouse model[4]
Dosage: 10-140 mg/kg Administration: Subcutaneous injection (s.c.) Result: decreased numbers of BALF neutrophil cells. Diminished levels of MMP-9, chemokines (CXCL-1, CXCL-2, and CCL-2) and pro-inflammatory cytokines (TNF-α, IL-6, IL-1β, and GM-CSF) in mouse lung tissue. Pharmacokinetics Study: Female BALB/c mice received a single SC injection of lefamulin at 35 mg/kg, dissolved in 0.9% saline. Plasma and bronchoalveolar lavage fluid (BALF) samples were collected at multiple time points (0.08 to 24 hours) post-dose. [4] Anti-inflammatory Efficacy Study (LPS-induced lung neutrophilia): Six-week-old male BALB/c mice were used. Lefamulin was dissolved in 0.9% saline. Doses of 10, 30, 35, 70, 100, and 140 mg/kg (free base equivalent) were administered subcutaneously in a volume of 10 mL/kg, 30 minutes before intranasal challenge with 5 μg LPS/50 μL saline. Animals were euthanized 4 hours post-LPS challenge. BALF was collected for total and differential neutrophil cell count analysis via an automated hematology analyzer. Lungs were harvested, homogenized in PBS with protease inhibitors, and centrifuged. The supernatants were analyzed for cytokines, chemokines, and MMP-9 using Luminex multiplex assay or ELISA kits. [4] |
| ADME/Pharmacokinetics |
Lefamoline showed good tissue penetration, especially in epithelial lining fluid and tissues associated with sexually transmitted infections (e.g., prostate, pelvic tissue). [2]
This article cites pharmacokinetic data from phase II/III studies of skin infections and pneumonia, but does not elaborate on them. [2] |
| Toxicity/Toxicokinetics |
Effects During Pregnancy and Lactation
◉ Overview of Use During Lactation There is currently no information regarding the use of lefamolin during lactation. The manufacturer recommends that mothers avoid breastfeeding during treatment and for two days after the last dose. Especially when breastfeeding newborns or premature infants, alternative medications are recommended. ◉ Effects on Breastfed Infants No published information found as of the revision date. ◉ Effects on Lactation and Breast Milk No published information found as of the revision date. |
| References | |
| Additional Infomation |
See also: Lefamorin (note moved here).
Drug Indications Xenleta can be used to treat adult CAP when conventionally recommended antibiotics for initial treatment of community-acquired pneumonia (CAP) are inappropriate or have failed. Official guidelines for the rational use of antibiotics should be consulted. Lefamorin is a novel truncated pleurotin antibiotic that binds to the peptidyl transferase center of the bacterial ribosome via hydrogen bonds and interactions at the A and P sites, thereby inhibiting bacterial protein synthesis, leading to conformational changes and enhanced binding. [2] Its unique mechanism of action minimizes cross-resistance with other antibiotics. [2] It is available in intravenous and oral formulations. [2] It is recommended as a first-line antibiotic for the treatment of sexually transmitted infections, including gonorrhea, non-gonococcal urethritis, and cervicitis, and may also be effective against pelvic inflammatory disease if its effectiveness against anaerobic bacteria is confirmed. [2] |
| Molecular Formula |
C28H45NO5S
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|---|---|
| Molecular Weight |
507.725607633591
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| Exact Mass |
507.302
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| Elemental Analysis |
C, 66.24; H, 8.93; N, 2.76; O, 15.76; S, 6.31
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| CAS # |
1061337-51-6
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| Related CAS # |
Lefamulin acetate;1350636-82-6
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| PubChem CID |
25185057
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| Appearance |
Solid powder
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| LogP |
4.567
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
7
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| Rotatable Bond Count |
6
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| Heavy Atom Count |
35
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| Complexity |
851
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| Defined Atom Stereocenter Count |
11
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| SMILES |
S([C@@H]1CC[C@H](C[C@H]1O)N)CC(=O)O[C@@H]1C[C@](C=C)(C)[C@H]([C@H](C)[C@]23CCC([C@H]2[C@@]1(C)[C@H](C)CC3)=O)O
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| InChi Key |
KPVIXBKIJXZQJX-FCEONZPQSA-N
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| InChi Code |
InChI=1S/C28H45NO5S/c1-6-26(4)14-22(34-23(32)15-35-21-8-7-18(29)13-20(21)31)27(5)16(2)9-11-28(17(3)25(26)33)12-10-19(30)24(27)28/h6,16-18,20-22,24-25,31,33H,1,7-15,29H2,2-5H3/t16-,17+,18-,20-,21-,22-,24+,25+,26-,27+,28+/m1/s1
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| Chemical Name |
(3aR,4R,5R,7S,8S,9R,9aS,12R)-8-hydroxy-4,7,9,12-tetramethyl-3-oxo-7-vinyldecahydro-4,9a-propanocyclopenta[8]annulen-5-yl 2-(((1R,2R,4R)-4-amino-2-hydroxycyclohexyl)thio)acetate
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| Synonyms |
BC-3781; BC 3781; BC3781
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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 | 1.9696 mL | 9.8478 mL | 19.6955 mL | |
| 5 mM | 0.3939 mL | 1.9696 mL | 3.9391 mL | |
| 10 mM | 0.1970 mL | 0.9848 mL | 1.9696 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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