Sitafloxacin
(Synonyms: 西他沙星; DU6859a) 目录号 : GC15081
西他沙星是一种新的氟喹诺酮类药物，具有更广的抗菌谱，作为广谱抗菌剂，对革兰氏阳性、革兰氏阴性和非典型病原体具有比氧氟沙星等其他喹诺酮类药物更强的活性, CPFX 和司帕沙星.西他沙星比其他喹诺酮类抗生素更能抑制 TNFα 的产生。
Cas No.:127254-12-0
Sample solution is provided at 25 µL, 10mM.
;)
,-1-7$$$37316672.jpg');)
;)
;)
$$$36806353.jpg');)
;33(7)%EF%BC%9A546-561$$$37156877.jpg');)
;)
;)
;)
%201124-1138.$$$35908550.jpg');)
%20766-780.$$$37100057.jpg');)
%20418-432.$$$36893736.jpg');)
%EF%BC%9A-240-255.$$$35108512.jpg');)
533-545$$$36543525.jpg');)
%201-13.$$$36600053.jpg');)
;)
Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
| Cell experiment [1]: | |
|
Cell lines |
LPS-stimulated THP-1 cells |
|
Preparation Method |
THP-1 cells were cultured with LPS in the presence or absence of antibiotics (Sitafloxacin) for 4 h. Following the incubation, supernatants were collected. |
|
Reaction Conditions |
1-50 µg/mL Sitafloxacin for 4h |
|
Applications |
Sitafloxacin significantly reduced the concentration of TNFα in the supernatants of LPS-stimulated THP-1 cells than other quinolone antibiotics did; Sitafloxacin also reduced the levels of IL-8, IP-10, MCP-1, MIP-1α and MIP-1β. |
| Animal experiment [2]: | |
|
Animal models |
Six-week-old male, ddY, specific-pathogen-free mice (body weight 16-20 g) |
|
Preparation Method |
From 24 h after infection, antibiotics were administered orally twice a day to the Sitafloxacin and CPFX treatment groups for 3 days.Each single dose was 10 mg/kg |
|
Dosage form |
10 mg/kg Sitafloxacin twice a day for 3 days |
|
Applications |
In Sitafloxacin-treated mice, H. influenzae was decreased by 3 days after starting oral administration of Sitafloxacin. |
|
References: [1]. Sakamaki I, Fukushi M, et,al. Sitafloxacin reduces tumor necrosis factor alpha (TNFα) converting enzyme (TACE) phosphorylation and activity to inhibit TNFα release from lipopolysaccharide-stimulated THP-1 cells. Sci Rep. 2021 Dec 17;11(1):24154. doi: 10.1038/s41598-021-03511-5. PMID: 34921186; PMCID: PMC8683466. [2]. Nakamura S, Yanagihara K, et,al. In vivo efficacy of sitafloxacin in a new murine model of non-typeable Haemophilus influenzae pneumonia by sterile intratracheal tube. Int J Antimicrob Agents. 2009 Sep;34(3):210-4. doi: 10.1016/j.ijantimicag.2009.03.011. Epub 2009 Apr 24. PMID: 19394203. |
|
Sitafloxacin is a new fluoroquinolone offering a broader spectrum , as a broad-spectrum antimicrobial agent[2],has more potent activity against Gram-positive, Gramnegative and atypical pathogens than other quinolones such as ofloxacin, CPFX and sparfloxacin[7,8].
Sitafloxacin suppressed TNFα production more strongly than the other quinolone antibiotics. It did not suppress the signaling pathways that produced TNFα but increased phosphorylated ERK. Sitafloxacin inhibited the extracellular release of TNFα[5,6].TACE specifically cleaves pro-TNFα to release TNFα from cell. Sitafloxacin reduced the phosphorylation and activity of TACE[1]. Sitafloxacin is effective against pneumococcal infections, and incidence of drug-resistant mutants is low in vitro conditions[3].
Sitafloxacin was effective against Haemophilus influenzae pneumonia in a murine model. In Sitafloxacin-treated mice, H. influenzae was decreased by 3 days after starting oral administration of Sitafloxacin, total cell counts and neutrophil counts in BALF were considerably decreased, and histopathologically inflammatory changes were greatly improved with Sitafloxacin treatment [4]. Sitafloxacin can achieve a higher tissue concentration than CPFX[9]. Besides, Sitafloxacin monotherapy might be effective against low-risk FN in lung cancer patients[10].
References:
[1]: Sakamaki I, Fukushi M, et,al. Sitafloxacin reduces tumor necrosis factor alpha (TNFα) converting enzyme (TACE) phosphorylation and activity to inhibit TNFα release from lipopolysaccharide-stimulated THP-1 cells. Sci Rep. 2021 Dec 17;11(1):24154. doi: 10.1038/s41598-021-03511-5. PMID: 34921186; PMCID: PMC8683466.
[2]: Sato K, Hoshino K, et,al. Antimicrobial activity of DU-6859, a new potent fluoroquinolone, against clinical isolates. Antimicrob Agents Chemother. 1992 Jul;36(7):1491-8. doi: 10.1128/AAC.36.7.1491. PMID: 1324647; PMCID: PMC191610.
[3]: Onodera Y, Uchida Y, et,al. Dual inhibitory activity of sitafloxacin (DU-6859a) against DNA gyrase and topoisomerase IV of Streptococcus pneumoniae. J Antimicrob Chemother. 1999 Oct;44(4):533-6. doi: 10.1093/jac/44.4.533. PMID: 10588315.
[4]: Nakamura S, Yanagihara K, et,al. In vivo efficacy of sitafloxacin in a new murine model of non-typeable Haemophilus influenzae pneumonia by sterile intratracheal tube. Int J Antimicrob Agents. 2009 Sep;34(3):210-4. doi: 10.1016/j.ijantimicag.2009.03.011. Epub 2009 Apr 24. PMID: 19394203.
[5]: Black RA, Rauch CT, et,al. A metalloproteinase disintegrin that releases tumour-necrosis factor-alpha from cells. Nature. 1997 Feb 20;385(6618):729-33. doi: 10.1038/385729a0. PMID: 9034190.
[6]: Moss ML, Jin SL, et,al. Cloning of a disintegrin metalloproteinase that processes precursor tumour-necrosis factor-alpha. Nature. 1997 Feb 20;385(6618):733-6. doi: 10.1038/385733a0. Erratum in: Nature 1997 Apr 17;386(6626):738. PMID: 9034191.
[7]: Milatovic D, Schmitz FJ, et,al. In vitro activities of sitafloxacin (DU-6859a) and six other fluoroquinolones against 8,796 clinical bacterial isolates. Antimicrob Agents Chemother. 2000 Apr;44(4):1102-7. doi: 10.1128/AAC.44.4.1102-1107.2000. PMID: 10722524; PMCID: PMC89825.
[8]: Miyashita N, Niki Y, et,al. In vitro and in vivo activities of sitafloxacin against Chlamydia spp. Antimicrob Agents Chemother. 2001 Nov;45(11):3270-2. doi: 10.1128/AAC.45.11.3270-3272.2001. PMID: 11600398; PMCID: PMC90824.
[9]: Fukuda Y, Yanagihara K, et,al. In vivo efficacies and pharmacokinetics of DX-619, a novel des-fluoro(6) quinolone, against Streptococcus pneumoniae in a mouse lung infection model. Antimicrob Agents Chemother. 2006 Jan;50(1):121-5. doi: 10.1128/AAC.50.1.121-125.2006. PMID: 16377676; PMCID: PMC1346772.
[10]: On R, Matsumoto T, et,al. Lung Oncology Group in Kyushu (LOGIK). Efficacy and Safety of Sitafloxacin in Treating Low-risk Febrile Neutropenia in Patients with Lung Cancer. JMA J. 2022 Jul 15;5(3):334-340. doi: 10.31662/jmaj.2021-0227. Epub 2022 May 23. PMID: 35992295; PMCID: PMC9358298.
西他沙星是一种新的氟喹诺酮类药物,具有更广的抗菌谱,作为广谱抗菌剂[2],对革兰氏阳性、革兰氏阴性和非典型病原体具有比氧氟沙星等其他喹诺酮类药物更强的活性, CPFX 和司帕沙星[7,8].
西他沙星比其他喹诺酮类抗生素更能抑制 TNFα 的产生。它不抑制产生 TNFα 的信号通路,但会增加磷酸化的 ERK。 Sitafloxacin 抑制 TNFα 的细胞外释放[5,6]。TACE 特异性切割 pro-TNFα 以从细胞中释放 TNFα。西他沙星降低 TACE[1] 的磷酸化和活性。西他沙星对肺炎球菌感染有效,体外条件下耐药突变发生率低[3]。
在小鼠模型中,西他沙星对流感嗜血杆菌肺炎有效。在西他沙星治疗的小鼠中,开始口服西他沙星后 3 天,流感嗜血杆菌减少,BALF 中的总细胞计数和中性粒细胞计数显着降低,组织病理学炎症变化在西他沙星治疗后得到极大改善 [4]。西他沙星可达到比 CPFX 更高的组织浓度[9]。此外,西他沙星单药治疗可能对肺癌患者的低危 FN 有效[10]。
| Cas No. | 127254-12-0 | SDF | |
| 别名 | 西他沙星; DU6859a | ||
| 化学名 | 7-[(7S)-7-amino-5-azaspiro[2.4]heptan-5-yl]-8-chloro-6-fluoro-1-[(1R,2S)-2-fluorocyclopropyl]-4-oxoquinoline-3-carboxylic acid | ||
| Canonical SMILES | C1CC12CN(CC2N)C3=C(C=C4C(=C3Cl)N(C=C(C4=O)C(=O)O)C5CC5F)F | ||
| 分子式 | C19H18ClF2N3O3 | 分子量 | 409.81 |
| 溶解度 | DMF: slightly soluble,DMSO: slightly soluble,Methanol: slightly soluble | 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。 |
||
| 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 | |||
 |
1 mg | 5 mg | 10 mg |
| 1 mM | 2.4402 mL | 12.2008 mL | 24.4016 mL |
| 5 mM | 0.488 mL | 2.4402 mL | 4.8803 mL |
| 10 mM | 0.244 mL | 1.2201 mL | 2.4402 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。
Sitafloxacin for Third-Line Helicobacter pylori Eradication: A Systematic Review
Background and aim: Sitafloxacin-based therapy is a potent candidate for third-line Helicobacter pylori eradication treatment. In this systematic review, we summarise current reports with sitafloxacin-based therapy as a third-line treatment. Methods: Clinical studies were systematically searched using PubMed, Cochrane library, Web of Science, and the Igaku-Chuo-Zasshi database. We combined data from clinical studies using a random-effects model and calculated pooled event rates, 95% confidence intervals (CIs), and the pooled odds ratio (OR). Results: We included twelve clinical studies in the present systematic review. The mean eradication rate for 7-day regimens of either PPI (proton pump inhibitor) or vonoprazan-sitafloxacin-amoxicillin was 80.6% (95% CI, 75.2-85.0). The vonoprazan-sitafloxacin-amoxicillin regimen was significantly superior to the PPI-sitafloxacin-amoxicillin regimen (pooled OR of successful eradication: 6.00; 95% CI: 2.25-15.98, p < 0.001). The PPI-sitafloxacin-amoxicillin regimen was comparable with PPI-sitafloxacin-metronidazole regimens (pooled OR: 1.06; 95% CI: 0.55-2.07, p = 0.86). Conclusions: Although the 7-day regimen composed of vonoprazan, sitafloxacin, and amoxicillin is a good option as the third-line Helicobacter pylori eradication treatment in Japan, the extension of treatment duration should be considered to further improve the eradication rate. Considering the safety concern of fluoroquinolones, sitafloxcin should be used after confirming drug susceptibility.
Sitafloxacin: in bacterial infections
Sitafloxacin is a fluoroquinolone antibacterial with in vitro activity against a broad range of Gram-positive and -negative bacteria, including anaerobic bacteria, as well as against atypical pathogens. It is approved in Japan for use in a number of bacterial infections caused by sitafloxacin-susceptible strains of Staphylococcus spp., Streptococcus pneumoniae, other Streptococcus spp., Enterococcus spp., Moraxella catarrhalis, Escherichia coli, Citrobacter spp., Klebsiella spp., Enterobacter spp., Serratia spp., Proteus spp., Morganella morganii, Haemophilus influenzae, Pseudomonas aeruginosa, Legionella pneumophila, Peptostreptococcus spp., Prevotella spp., Porphyromonas spp., Fusobacterium spp., Chlamydia trachomatis, Chlamydophila pneumoniae and Mycoplasma pneumoniae. In terms of clinical efficacy, oral sitafloxacin was noninferior to oral levofloxacin in the treatment of community-acquired pneumonia or an infectious exacerbation of chronic respiratory tract disease, noninferior to oral tosufloxacin in the treatment of community-acquired pneumonia, and noninferior to oral levofloxacin in the treatment of complicated urinary tract infections, according to the results of randomized, double-blind, multicentre, noninferiority trials. Noncomparative studies demonstrated the efficacy of oral sitafloxacin in otorhinolaryngological infections, urethritis in men, C. trachomatis-associated cervicitis in women and odontogenic infections. Gastrointestinal disorders and laboratory abnormalities were the most commonly occurring adverse reactions in patients receiving oral sitafloxacin. Adverse reactions reported in sitafloxacin recipients in the active comparator trials were of mild to moderate severity.
Sitafloxacin Expresses Potent Anti- Mycobacterium abscessus Activity
Therapeutic options for treating Mycobacterium abscessus infections are extremely limited; quinolones are important. The in vitro anti-M. abscessus activities of nine quinolones, emphasizing sitafloxacin, were investigated. Antimicrobial susceptibility testing was performed on 10 non-tuberculous mycobacterium reference strains and 194 clinical, M. abscessus isolates. The activity of sitafloxacin against intracellular M. abscessus residing within macrophages was also evaluated. A checkerboard assay was conducted to determine synergy between sitafloxacin and 10 clinically important antibiotics. Among the nine quinolones tested, sitafloxacin exhibited the greatest anti-M. abscessus activity with MIC50 and MIC90 of 1 and 2 mg/L, respectively. Sitafloxacin exerted a bacteriostatic effect on M. abscessus and inhibited the intracellular growth of M. abscessus at concentrations equivalent to clarithromycin. No antagonism between sitafloxacin and 10 clinically important anti-M. abscessus antibiotics was evident. In summary, sitafloxacin exhibited a significant advantage relative to other quinolones in inhibiting the growth of M. abscessus in vitro, suggesting the potential inclusion of sitafloxacin in new strategies to treat M. abscessus infections.
Sitafloxacin hydrate for bacterial infections
Sitafloxacin hydrate (DU-6859a, Gracevit), a new-generation, broad-spectrum oral fluoroquinolone that is very active against many Gram-positive, Gram-negative and anaerobic clinical isolates, including strains resistant to other fluoroquinolones, was recently approved in Japan for the treatment of respiratory and urinary tract infections. Sitafloxacin is active against methicillin-resistant staphylococci, Streptococcus pneumoniae and other streptococci with reduced susceptibility to levofloxacin and other quinolones and enterococci. Sitafloxacin has also demonstrated activity against clinical isolates of Klebsiella pneumoniae (including about 67% of strains producing extended-spectrum, beta-lactamases and resistant to ciprofloxacin), Enterobacter cloacae, Pseudomonas aeruginosa with some activity against quinolone-resistant strains and Acinetobacter baumannii. The in vitro activity against anaerobes is comparable to imipenem or metronidazole. In a published phase II randomized, open-label, multicenter study of patients hospitalized with pneumonia, sitafloxacin (400 mg once daily) was comparable to imipenem/cilastatin (500 mg three times a day). Results of the phase III trials of sitafloxacin are not available in English. The clinical safety profile of sitafloxacin has been characterized from 1,059 patients who participated in 10 clinical trials. The most common events with 50 or 100 mg twice daily were gastrointestinal disorders (17.2%), mostly diarrhea, and abnormal laboratory test results (16.2%), mostly liver enzyme elevations. For Japanese patients, sitafloxacin provides the broad-spectrum coverage promised by clinafloxacin and trovafloxacin and comparable to carbapenems. While it is currently limited by its potential for phototoxicity in Caucasians, phototoxicity is essentially irrelevant if sitafloxacin is used in hospitals and especially in intensive care units.
A randomized, active-controlled, multicentre clinical trial to evaluate the efficacy and safety of oral sitafloxacin versus levofloxacin in Chinese adults with acute uncomplicated or complicated urinary tract infection
Purpose: To evaluate the efficacy and safety of oral sitafloxacin versus levofloxacin in Chinese adults with acute uncomplicated urinary tract infection (UTI) or complicated UTI.
Methods: In this randomized, active-controlled clinical trial, the patients with acute uncomplicated UTI were randomized to receive sitafloxacin 100-mg once-daily (qd) or levofloxacin 500-mg qd orally for 3-5 days. The patients with complicated UTI were randomized to receive sitafloxacin 100-mg twice daily or levofloxacin 500-mg qd orally for 10-14 days. The primary endpoint was the clinical efficacy at test-of-cure (TOC) visit.
Results: At TOC visit, the clinical cure rate was 89.2% (58/65) in sitafloxacin group and 97.1% (68/70) in levofloxacin group for the patients with acute uncomplicated UTI corresponding to the bacterial eradication rate of 97.1% (34/35) and 97.6% (41/42) (all p > .05), respectively. For the patients with complicated UTI, the clinical cure rate was 81.8% (27/33) in sitafloxacin group and 76.9% (20/26) in levofloxacin group corresponding to the bacterial eradication rate of 93.3% (14/15) and 63.6% (7/11) (all p > .05), respectively. Sitafloxacin and levofloxacin showed similar incidence of drug-related adverse events.
Conclusions: Oral sitafloxacin is as effective and safe as levofloxacin in treating acute uncomplicated and complicated UTI. KEY MESSAGE: Oral sitafloxacin showed similar clinical cure rate and bacterial eradication rate as levofloxacin for treatment of complicated and uncomplicated urinary tract infections (UTIs) in a randomized, active-controlled, multicentre clinical trial. Oral sitafloxacin is safe and well-tolerated in treating acute uncomplicated and complicated UTIs in Chinese adults. Sitafloxacin is a promising alternative treatment option for UTIs in adults.