Ceftobiprole (Ro 63-9141)
(Synonyms: 头孢吡普; Ro 63-9141; BAL 9141) 目录号 : GC32128
Ceftobiprole (Ro 63-9141) (Ro 63-9141) 是一种广谱头孢菌素，对甲氧西林 (MRSA) 和耐万古霉素葡萄球菌 (VRSA) 和耐青霉素链球菌具有高水平的体外活性，MIC90 值为2 μ；MRSA 的克/毫升。
Cas No.:209467-52-7
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: >95.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Ceftobiprole is a broad-spectrum cephalosporin with activity against Methicillin-resistant staphylococcus aureus (MRSA) with the MIC90 value of 2 mcg/mL.
Ceftobiprole has demonstrates activity against important gram-positive bacteria, including penicillin-resistant S. pneumonia (PRSP), Methicillin-resistant S. aureus (MRSA), and E. faecalis with MIC90 values of 0.25, 2, and 2 mcg/mL, respectively. Ceftobiprole has also demonstrated potent in vitro activity against several clinical isolates of community-associated Methicillin-resistant S. aureus (CA-MRSA), vancomycin-intermediate S. aureus (VISA), and Vancomycin-resistant S. aureus (VRSA), with a minimum inhibitory concentration (MIC) of 2 mcg/mL[1]. Ceftobiprole is highly active against S. aureus, withMICs ranging from 0.12 to 4 mg/L (only one resistant strain,MIC of 4 mg/L). Furthermore, Ceftobiprole is twice more active on Methicillin-susceptible S. aureus (MSSA) strains with MIC50 and MIC90 of 0.5 mg/L than on MRSA strains with MIC50 and MIC90 of 1 mg/L. Moreover, Panton-Valentine leukocidin (PVL)+MRSA are slightly more susceptible to Ceftobiprole (MIC50 of 0.5 mg/L and MIC90 of 1 mg/L) than PVL-MRSA (MIC50 and MIC90 of 1 mg/L)[2].
[1]. Kisgen J, et al. Ceftobiprole, a Broad-Spectrum Cephalosporin With Activity against Methicillin-Resistant Staphylococcus aureus (MRSA). P T. 2008 Nov;33(11):631-41. [2]. Hodille E, et al. In vitro activity of ceftobiprole on 440 Staphylococcus aureus strains isolated from bronchopulmonary infections. Med Mal Infect. 2017 Mar;47(2):152-157.
| Cas No. | 209467-52-7 | SDF | |
| 别名 | 头孢吡普; Ro 63-9141; BAL 9141 | ||
| Canonical SMILES | O=C(C(N12)=C(/C=C3C(N([C@H]4CNCC4)CC/3)=O)CS[C@]2([H])[C@H](NC(/C(C5=NSC(N)=N5)=N\O)=O)C1=O)O | ||
| 分子式 | C20H22N8O6S2 | 分子量 | 534.57 |
| 溶解度 | DMSO : 5 mg/mL (9.35 mM) | 储存条件 | Store at -20°C,unstable in solution, ready to use. |
| 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 | 1.8707 mL | 9.3533 mL | 18.7066 mL |
| 5 mM | 0.3741 mL | 1.8707 mL | 3.7413 mL |
| 10 mM | 0.1871 mL | 0.9353 mL | 1.8707 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。
Ceftobiprole Medocaril: BAL5788, JNJ 30982081, JNJ30982081, RO 65-5788, RO 655788
Drugs R D 2006;7(5):305-11.PMID:16922591DOI:10.2165/00126839-200607050-00003.
Ceftobiprole medocaril [BAL 5788, RO 65-5788, JNJ 30982081] is a prodrug in phase III clinical development with Basilea Pharmaceutica and Cilag AG (Johnson & Johnson) for the potential treatment of serious bacterial infections, including methicillin-resistant Staphylococcus aureus (MRSA). Ceftobiprole medocaril is the water-soluble prodrug of the pyrrolidinone cephalosporin, Ceftobiprole [BAL 9141, Ro 63-9141]. Because of the low water solubility of Ceftobiprole, its clinical application was limited and Basilea began its investigations into Ceftobiprole medocaril for further development. Ceftobiprole medocaril is being developed for IV administration and is currently undergoing phase III trials for complicated skin and skin structure infections (including MRSA) and hospital-acquired (nosocomial) pneumonia. Ceftobiprole medocaril has a broad spectrum of activity against Gram-positive bacteria (including methicillin-resistant staphylococci, penicillin-resistant pneumococci and Enterococcus faecalis) and Gram-negative bacteria. Ceftobiprole medocaril inhibits all transpeptidases, including the penicillin-binding protein (PBP) 2a, by a unique combination of features. PBP 2a is the primary enzyme responsible for beta-lactam drug resistance in MRSA; PBP 2a also acts as a key defense mechanism by interacting with the bacterial cell wall to form a chemical barricade that is impervious to antibiotics. Ceftobiprole medocaril has been designed specifically to bind to this penicillin-resistant target. Ceftobiprole medocaril is bactericidal and has not shown resistance development in vitro or in stringent animal models. Studies conducted by Basilea have demonstrated that Ceftobiprole medocaril is readily converted to Ceftobiprole, and shows markedly improved water solubility. In February 2005, Basilea Pharmaceutica AG entered into an exclusive worldwide agreement with Cilag AG International (Johnson & Johnson) to develop, manufacture and market Ceftobiprole medocaril. Ortho-McNeil Pharmaceutical (Johnson & Johnson) will market Ceftobiprole medocaril in the US, and its affiliate companies, known as Janssen-Cilag, will market the product outside the US (entered as World in the Licensee table). Basilea has retained an option to co-promote Ceftobiprole medocaril in the US, major European countries, Japan and China. Johnson & Johnson Pharmaceutical Research and Development LLC will develop Ceftobiprole medocaril in collaboration with Basilea. Roche previously retained an opt-in right on Ceftobiprole medocaril. However, following Roche's decision not to exercise this right in May 2004, Basilea gained full global commercialisation rights for Ceftobiprole medocaril. Roche retains its major shareholding in Basilea. Ceftobiprole medocaril is currently in phase III trials for complicated skin and skin structure infections due to MRSA, and nosocomial pneumonia (including ventilator-associated pneumonia) due to suspected or proven MRSA, and community-acquired pneumonia. The US FDA has granted fast-track status to the compound for these two indications. Phase III results are expected in 2006 and an NDA is expected to be submitted to the FDA in 2007. An additional pivotal phase III trial (STRAUSS 2, STudy of Resistant Staphyloccocus aureus in Skin and Skin structure infections) of Ceftobiprole medocaril was initiated in October 2005 for complicated skin infections, including diabetic foot infections. This trial will be conducted in conjunction with Johnson & Johnson Pharmaceutical Research and Development.
Ceftobiprole: an extended-spectrum anti-methicillin-resistant Staphylococcus aureus cephalosporin
Ann Pharmacother 2008 Jun;42(6):806-16.PMID:18477729DOI:10.1345/aph.1L016.
Objective: To summarize and evaluate the literature concerning Ceftobiprole. Data sources: Literature identification was conducted through MEDLINE (1966-February 2008) and International Pharmaceutical Abstracts (1970-February 2008) using the terms Ceftobiprole, medocaril, BAL 5788, RO-5788, BAL 9141, Ro 63-9141, pyrrolidinone cephalosporin, MRSA, complicated skin and skin-structure infections (cSSSIs), community-acquired pneumonia, and nosocomial pneumonia. Additional publications were identified through a review of articles and abstracts from infectious disease meetings. Study selection and data extraction: All articles in English were evaluated and all pertinent information was included. Data synthesis: Ceftobiprole medocaril is an extended-spectrum cephalosporin with activity against methicillin-resistant Staphylococcus spp., vancomycin-resistant Staphylococcus aureus, penicillin-resistant Streptococcus pneumoniae, vancomycin-resistant Enterococcus faecalis, Enterobacteriaceae, and Pseudomonas aeruginosa. Inactivity includes extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae and Enterococcus faecium. Preliminary data suggest that Ceftobiprole may be effective with a 1-hour infusion of 500 mg every 12 hours for gram-positive infections and 500 mg every 8 hours with a 2-hour infusion for polymicrobial infections. Two clinical trials support these dosing regimens for cSSSIs. Ceftobiprole was noninferior to vancomycin in suspected gram-positive cSSSIs, with cure rates of 93.3% and 93.5%, respectively. Furthermore, Ceftobiprole was noninferior to vancomycin and ceftazidime in polymicrobial cSSSIs (cure rates 90.5% vs 90.2%, respectively). Although the total number of adverse effects was similar to those of the comparator, more patients in the Ceftobiprole group experienced nausea, vomiting, and dysgeusia. Conclusions: The activity of Ceftobiprole and limited clinical data suggest that it may be useful as empiric monotherapy for cSSSI and in combination with other antimicrobials in lower respiratory tract infections for which Phase 3 clinical trials are currently exploring. Although not shown in vitro, Ceftobiprole may induce resistance due to its broad spectrum of activity. Approval is expected for the treatment of cSSSI.
Quality control guidelines for BAL9141 (Ro 63-9141), an investigational cephalosporin, when reference MIC and standardized disk diffusion susceptibility test methods are used
J Clin Microbiol 2004 Jul;42(7):3356-8.PMID:15243116DOI:10.1128/JCM.42.7.3356-3358.2004.
BAL9141 is a novel cephalosporin with a broad spectrum of activity, including activity against methicillin-resistant staphylococci. This multicenter study was performed to establish quality control (QC) guidelines for susceptibility testing of BAL9141 in phase 3 clinical trials and after U.S. Food and Drug Administration approval. The proposed 3 or 4 log(2) dilution MIC ranges encompass 97.8 to 100.0% of reported results, while the proposed 7- to 9-mm-zone-diameter QC ranges included 95.2 to 99.4% of the participant-reported disk diffusion results.
Ceftobiprole: a new broad spectrum cephalosporin
Expert Opin Pharmacother 2009 Jul;10(10):1675-86.PMID:19527192DOI:10.1517/14656560903048967.
Ceftobiprole, formerly designated BAL9141/Ro 63-9141, is a pyrrolidinone-3-ylidene-methyl cephalosporin with demonstrated in vitro activity against MRSA, Enterococcus faecalis, Enterobacteriaceae and Pseudomonas aeruginosa. Ceftobiprole has a low potential for inducing chromosomal AmpC beta-lactamases but it is hydrolyzed by most extended spectrum beta-lactamases and metallo-beta-lactamases. Glomerular filtration is predominantly responsible for removal of the free drug from the systemic circulation. The efficacy of Ceftobiprole in the treatment of complicated skin and ski-structure infections has been recently demonstrated in two Phase III randomized clinical trials involving 1600 patients. Two other Phase III clinical trials to assess Ceftobiprole's efficacy in community-acquired pneumonia and nosocomial pneumonia have also concluded. While the drug met the noninferiority criteria for community-acquired pneumonia and nosocomial pneumonia involving non-ventilator associated pneumonia, Ceftobiprole was less effective than the comparator in ventilator associated pneumonia subjects. Ceftobiprole was well tolerated with a safety profile consistent with the cephalosporin class of antibiotic. The most frequent drug-related adverse event was dysgeusia. Ceftobiprole is intended for use in the hospital for the treatment of infections that frequently involve beta-lactam-resistant Gram-negative and Gram-positive organisms.
BAL9141, a novel extended-spectrum cephalosporin active against methicillin-resistant Staphylococcus aureus in treatment of experimental endocarditis
Antimicrob Agents Chemother 2002 Jan;46(1):171-7.PMID:11751129DOI:10.1128/AAC.46.1.171-177.2002.
The therapeutic efficacy of BAL9141 (formerly Ro 63-9141), a novel cephalosporin with broad in vitro activity that also has activity against methicillin-resistant Staphylococcus aureus (MRSA), was investigated in rats with experimental endocarditis. The test organisms were homogeneously methicillin-resistant S. aureus strain COL transformed with the penicillinase-encoding plasmid pI524 (COL Bla+) and homogeneously methicillin-resistant, penicillinase-producing isolate P8-Hom, selected by serial exposure of parent strain P8 to methicillin. The MICs of BAL9141 for these organisms (2 mg/liter) were low, and BAL9141was bactericidal in time-kill curve studies after 24 h of exposure to either two, four, or eight times the MIC. Rats with experimental endocarditis were treated in a three-arm study with a continuous infusion of BAL5788 (formerly Ro 65-5788), a carbamate prodrug of BAL9141, or with amoxicillin-clavulanate or vancomycin. The rats were administered BAL9141 to obtain steady-state target levels of 20, 10, and 5 mg of per liter or were administered either 1.2 g of amoxicillin-clavulanate (ratio 5:1) every 6 h or 1 g of vancomycin every 12 h at changing flow rates to simulate the pharmacokinetics produced in humans by intermittent intravenous treatment. Treatment was started 12 h after bacterial challenge and lasted for 3 days. BAL9141 was successful in the treatment of experimental endocarditis due to either MRSA isolate COL Bla+ or MRSA isolate P8-Hom at the three targeted steady-state concentrations and sterilized >90% of cardiac vegetations (P < 0.005 versus controls; P < 0.05 versus amoxicillin-clavulanate and vancomycin treatment groups). These promising in vivo results with BAL9141 correlated with the high affinity of the drug for PBP 2a and its stability to penicillinase hydrolysis observed in vitro.