Levonadifloxacin
(Synonyms: (S)-(-)-Nadifloxacin; WCK 771) 目录号 : GC67773Levonadifloxacin ((S)-(-)-Nadifloxacin; WCK 771) 是一种广谱的抗葡萄球菌剂。Levonadifloxacin 对甲氧西林敏感的金黄色葡萄球菌 (MSSA) 和对甲氧西林耐药的金黄色葡萄球菌具有抗菌活性，减少单核细胞 THP-1 吞噬的 MRSA 和 MSSA 菌株。
Cas No.:154357-42-3
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Levonadifloxacin ((S)-(-)-Nadifloxacin; WCK 771) is a broad-spectrum anti-staphylococcal agent. Levonadifloxacin shows antibacterial activity against Methicillin -susceptible Staphylococcus aureus (MSSA) and Methicillin-resistant S. aureus (MRSA) strains, with a reduction of which phagocytized in THP-1 monocytes[1].
Levonadifloxacin (32 μg/mL; 24 h) achieves a 90-99% intracellular reduction of MSSA and MRSA strains phagocytized in THP-1 monocytes with MICs of 0.03 μg/mL and 15.0 ng/mL[1].
Levonadifloxacin (12.5-400 mg/kg; s.c.; single dose) shows efficacy in vivo against Staphylococcus aureus in a Neutropenic Murine Lung Infection Model[2].
| Animal Model: | Male/Female Swiss Albino mice (25-28 g) for plasma pharmacokinetic analyses[2] | ||||||||||||||||||||||||||||||||
| Dosage: | 12.5, 25, 50, 100, 200, 300 and 400 mg/kg | ||||||||||||||||||||||||||||||||
| Administration: | Subcutaneous injection; single dose; collected samples at 10 time points/dose (0.25, 0.5, 1, 2, 4, 6, 8, 10, 58 12 and 24 h post dose) | ||||||||||||||||||||||||||||||||
| Result: |
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[1]. Dubois J, et al. Levonadifloxacin (WCK 771) exerts potent intracellular activity against Staphylococcus aureus in THP-1 monocytes at clinically relevant concentrations. J Med Microbiol. 2019 Dec;68(12):1716-1722.
[2]. Bhagwat SS, et al. In Vivo Pharmacokinetic/Pharmacodynamic Targets of Levonadifloxacin against Staphylococcus aureus in a Neutropenic Murine Lung Infection Model. Antimicrob Agents Chemother. 2019 Jul 25;63(8):e00909-19.
| Cas No. | 154357-42-3 | SDF | Download SDF |
| 别名 | (S)-(-)-Nadifloxacin; WCK 771 | ||
| 分子式 | C19H21FN2O4 | 分子量 | 360.38 |
| 溶解度 | DMSO : 125 mg/mL (346.86 mM; Need ultrasonic) | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.7748 mL | 13.8742 mL | 27.7485 mL |
| 5 mM | 0.555 mL | 2.7748 mL | 5.5497 mL |
| 10 mM | 0.2775 mL | 1.3874 mL | 2.7748 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Levonadifloxacin, a Novel Broad-Spectrum Anti-MRSA Benzoquinolizine Quinolone Agent: Review of Current Evidence
Drug Des Devel Ther 2019 Dec 24;13:4351-4365.PMID:31920285DOI:10.2147/DDDT.S229882.
Levonadifloxacin and its prodrug alalevonadifloxacin are novel broad-spectrum anti-MRSA agents belonging to the benzoquinolizine subclass of quinolone, formulated for intravenous and oral administration, respectively. Various in vitro and in vivo studies have established their antimicrobial spectrum against clinically significant Gram-positive, Gram-negative, atypical, and anaerobic pathogens. The potent activity of Levonadifloxacin against MRSA, quinolone-resistant Staphylococcus aureus, and hetero-vancomycin-intermediate strains is an outcome of its well-differentiated mechanism of action involving preferential targeting to DNA gyrase. Potent anti-staphylococcal activity of Levonadifloxacin was also observed in clinically relevant experimental conditions such as acidic pH, the intracellular environment, and biofilms, suggesting that the drug is bestowed with enabling features for the treatment of difficult-to-treat MRSA infections. Levonadifloxacin also retains clinically relevant activity against resistant respiratory pathogens such as macrolide- and penicillin-resistant Streptococcus pneumoniae, Streptococcus pyogenes, Haemophilus influenzae, and Moraxella catarrhalis and, in conjunction with clinically established best-in-class human epithelial lung fluid concentration, has promising potential in the management of recalcitrant respiratory infections. Attractive features, such as resistance to NorA efflux, divergent mechanism of action in S. aureus, cidality against high-inoculum cultures, and low mutant prevention concentration, are likely to confer favorable resistance-suppression features to both agents. In vivo studies have shown promising efficacy in models of acute bacterial skin and skin structure infection, respiratory infections, pyelonephritis, and peritonitis at human-equivalent mouse doses. Both formulations were well tolerated in multiple phase I studies and overall showed a dose-dependent exposure. In particular, oral alalevonadifloxacin showed excellent bioavailability (~90%), almost mirroring the pharmacokinetic profile of intravenous Levonadifloxacin, indicating the prodrug's seamless absorption and efficient cleavage to release the active parent drug. Hepatic impairment studies showed that clinical doses of Levonadifloxacin/alalevonadifloxacin are not required to be adjusted for various degrees of hepatic impairment. With the successful completion of phase II and phase III studies for both Levonadifloxacin and alalevonadifloxacin, they represent clinically attractive therapeutic options for the treatment of infections caused by multi-drug-resistant Gram-positive organisms. Herein, we review the current evidence on therapeutically appealing attributes of Levonadifloxacin and alalevonadifloxacin, which are based on a range of non-clinical in vitro and in vivo investigations and clinical studies.
Chemistry, Biological Properties and Analytical Methods of Levonadifloxacin: A Review
Crit Rev Anal Chem 2022;52(5):1069-1077.PMID:33307757DOI:10.1080/10408347.2020.1855412.
Increased use of antibiotics globally has led to the threat of antibiotic resistance; this drove the urge of researchers toward discovering more potent and broad-spectrum antibiotics. Levonadifloxacin (LND) is the very first antibiotic developed by an Indian company Wockhardt. It is S (-) isomer of another broad-spectrum antibiotic Nadifloxacin which is used topically for skin, soft tissue bacterial infection. LND belongs to the benzo quinolizine category which is a subclass of fluoroquinolone, indicated for ABSSIS, CABP, and other infections including diabetic foot infection; formulated as l-arginine salt of Levonadifloxacin (WCK177) for IV and l-alanine ester mesylate salt as alalevonadifloxacin (WCK2349) for oral administration. It generally shows dominant antibacterial activity against Gram-negative, and positive bacterial infections, particularly toward methicillin-resistant Staphylococcus aureus (MRSA) by dual inhibition of DNA gyrase and topoisomerase IV. Producing quality product that complies to regulatory requirements is a big concern for pharma industries. To this context, validated analytical methods for routine quality control are essential for quantification of LND as an API alone and together with pharmaceutical formulations. This review suggests therapeutic, pharmacological, and analytical aspects regarding the novel drug LND and particularly focuses on discussing various reported analytical methods present for analytical or bioanalytical estimation of the drug and suggest to develop a simple and validated method which also complies to green chemistry.
Meeting the Unmet Need in the Management of MDR Gram-Positive Infections with Oral Bactericidal Agent Levonadifloxacin
Crit Care Res Pract 2022 Sep 9;2022:2668199.PMID:36785544DOI:10.1155/2022/2668199.
Levonadifloxacin (intravenous) and its oral prodrug alalevonadifloxacin are broad-spectrum antibacterial agents developed for the treatment of difficult-to-treat infections caused by multidrug-resistant Gram-positive bacteria, especially methicillin-resistant Staphylococcus aureus, atypical bacteria, anaerobic bacteria, and biodefence pathogens as well as Gram-negative bacteria. Levonadifloxacin has a well-defined mechanism of action involving a strong affinity for DNA gyrase as well as topoisomerase IV. Alalevonadifloxacin with widely differing solubility and oral bioavailability has pharmacokinetic profile identical to Levonadifloxacin. Unlike existing MRSA drugs such as vancomycin and linezolid, which cause unfavorable side effects like nephrotoxicity, bone-marrow toxicity, and muscle toxicity, Levonadifloxacin/alalevonadifloxacin has demonstrated superior safety and tolerability features with no serious adverse events. Levonadifloxacin/alalevonadifloxacin could be a useful weapon in the battle against infections caused by resistant microorganisms and could be a preferred antibiotic of choice for empirical therapy in the future.
India-discovered Levonadifloxacin & alalevonadifloxacin: A review on susceptibility testing methods, CLSI quality control and breakpoints along with a brief account of their emerging therapeutic profile as a novel standard-of-care
Indian J Med Microbiol 2023 Jan-Feb;41:71-80.PMID:36509611DOI:10.1016/j.ijmmb.2022.11.005.
Background: Levonadifloxacin (intravenous) and alalevonadifloxacin (oral prodrug) are novel antibiotics based on benzoquinolizine subclass of fluoroquinolone, licensed for clinical use in India in 2019. The active moiety, Levonadifloxacin, is a broad-spectrum antibiotic with a high potency against methicillin-resistant Staphylococcus. aureus, multi-drug resistant pneumococci and anaerobes. Objective: This review, for the first time, critically analyses the antimicrobial susceptibility testing methods, Clinical Laboratory & Standards Institute (CLSI)-quality control of susceptibility testing and breakpoints of Levonadifloxacin. Further, the genesis, discovery and developmental aspects as well as therapeutic profile of Levonadifloxacin and alalevonadifloxacin are briefly described. Contents: In order to aid the scientific and clinician communities with a single comprehensive overview on all the key aspects of Levonadifloxacin and alalevonadifloxacin, the present article covers the reference MIC and disk diffusion methods for Levonadifloxacin susceptibility testing that were approved by CLSI and the reference ranges for quality control strains published in the CLSI M100 document. The breakpoints of Levonadifloxacin were derived in concordance to US FDA, European Committee on Antibiotic Susceptibility Testing (EUCAST) and CLSI approaches. Further, the article provides a brief account of challenges encountered during the discovery stages of Levonadifloxacin and alalevonadifloxacin, activity spectrum and safety benefits accruing from structural novelty-linked mechanism of action. Further, the review also covers in vitro and in vivo activities, registrational clinical studies and patient-friendly features of Levonadifloxacin/alalevonadifloxacin. Cumulatively, Levonadifloxacin has a potential to offer a long awaited new standard-of-care treatment for the resistant Gram-positive bacterial infections.
Preclinical safety evaluation of Levonadifloxacin, a novel anti-methicillin-resistant Staphyloccocus aureus benzoquinolizine fluoroquinolone by intravenous and oral administration
J Appl Toxicol 2022 Aug;42(8):1354-1370.PMID:35146781DOI:10.1002/jat.4300.
Fluoroquinolone (FQ) antibacterials have drawn heightened attention from various international regulatory agencies due to their class-specific side effects. Levonadifloxacin is a novel broad spectrum benzoquinolizine FQ active against methicillin-resistant Staphyloccocus aureus (MRSA). Owing to FQ-associated safety concerns, extensive preclinical safety pharmacology (central nervous system and cardiac safety) and toxicology studies (subacute repeat-dose toxicity, genotoxicity, phototoxicity and chondrotoxicity) of Levonadifloxacin were performed at relatively high doses. Intravenous (IV) and oral studies were conducted using WCK 771 (l-arginine salt of Levonadifloxacin) and WCK 2349 (l-alanine ester prodrug of Levonadifloxacin), respectively. Safety pharmacology studies following single dose revealed no adverse effects on central nervous system (including seizure) in mice and cardiovascular system (hERG and monkey telemetry). In repeat-dose toxicity studies, except for IV bolus dosing related effects in rat (hyperactivity, mild convulsion, polypnoea and injection site irritation) and dog (emesis and salivation), no other adverse findings limiting the dosing duration were observed. No major biochemical, haematological, gross or histopathological changes suggestive of damage to vital organs were observed in either WCK 771- or WCK 2349-treated groups. WCK 771 and WCK 2349 were found to be nongenotoxic; however, they showed weak phototoxicity that was comparable with levofloxacin. WCK 771 showed chondrotoxicity in the Beagle dog pups on repeat-dose administration; however, the severity level was lower than ofloxacin. Overall, preclinical safety studies helped establish wider safety margin for WCK 771 and WCK 2349 that supports administration of higher therapeutic doses in humans by both IV and oral routes, thereby enabling safe anti-MRSA treatment.