T-91825
(Synonyms: PPI-0903M) 目录号 : GC63208
T-91825 (PPI-0903M) 是一种 N-膦酰基型头孢菌素，是 TAK-599 的活性形式。T-91825 对革兰氏阳性菌和革兰氏阴性菌均有活性。
Cas No.:189345-04-8
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >96.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
T-91825 (PPI-0903M), an N-phosphono-type cephalosporin, is the active form of TAK-599. T-91825 is active against both gram-positive and gram-negative bacteria[1][2].
PPI-0903M is very active against S. aureus (MIC50=0.25 μg/mL), including methicillin-resistant (MRSA) strains (MIC50=1 μg/mL)[1].PPI-0903M is active against hetero-vancomycin-intermediate S. aureus (100 strains), with MIC50s ranging from 0.25 to 4 μg/mL[1].
AK-599 (20 mg/kg; s.c. three times a day for 2 days) decreases the bacterial cell counts in lungs more than 99.9% in a mouse pneumonia model caused by MRSA[2].
[1]. Sader HS, et, al. Antimicrobial activity and spectrum of PPI-0903M (T-91825), a novel cephalosporin, tested against a worldwide collection of clinical strains. Antimicrob Agents Chemother. 2005 Aug;49(8):3501-12.
[2]. Iizawa Y, et, al. In vitro antimicrobial activity of T-91825, a novel anti-MRSA cephalosporin, and in vivo anti-MRSA activity of its prodrug, TAK-599. J Infect Chemother. 2004 Jun;10(3):146-56.
| Cas No. | 189345-04-8 | SDF | |
| 别名 | PPI-0903M | ||
| 分子式 | C22H20N8O5S4 | 分子量 | 604.7 |
| 溶解度 | DMSO : 100 mg/mL (165.37 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 | 1.6537 mL | 8.2686 mL | 16.5371 mL |
| 5 mM | 0.3307 mL | 1.6537 mL | 3.3074 mL |
| 10 mM | 0.1654 mL | 0.8269 mL | 1.6537 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。
In vitro antimicrobial activity of T-91825, a novel anti-MRSA cephalosporin, and in vivo anti-MRSA activity of its prodrug, TAK-599
J Infect Chemother 2004 Jun;10(3):146-56.PMID:15290453DOI:10.1007/s10156-004-0309-3.
TAK-599 is a water-soluble prodrug of a cephalosporin compound, T-91825. In vitro and in vivo antibacterial activities of T-91825 and TAK-599, respectively, were examined. T-91825 was active against both gram-positive and gram-negative bacteria, unlike vancomycin and linezolid, which are inactive against gram-negative bacteria. The 90% minimum inhibitory concentration of T-91825 against clinical isolates of methicillin-resistant Staphylococcus aureus (MRSA) was 2 micro g/ml. This activity was comparable to those of vancomycin, linezolid, teicoplanin, and arbekacin. T-91825 was similarly active against vancomycin-intermediate S. aureus. In a time-kill study, T-91825 showed more rapid and distinct decrease of viable cells of two MRSA strains than did vancomycin and linezolid in vitro. The effect of TAK-599 against systemic infection caused by clinical isolates of MRSA in mice was comparable or superior to that of vancomycin, linezolid, teicoplanin, and arbekacin. In addition, TAK-599 at a dose of 20 mg/kg significantly decreased bacterial counts in lungs of mice in an experimental pneumonia model caused by MRSA in which vancomycin and linezolid were totally ineffective at the same dose. These results suggest the usefulness of TAK-599 in the treatment of MRSA infections in humans.
In vitro activity of ceftaroline (PPI-0903M, T-91825) against bacteria with defined resistance mechanisms and phenotypes
J Antimicrob Chemother 2007 Aug;60(2):300-11.PMID:17548456DOI:10.1093/jac/dkm150.
Background: Ceftaroline (PPI-0903M, T-91825) is a novel cephalosporin, administered as an N-phosphono prodrug. We investigated its in vitro activity and resistance selection potential. Methods: MICs were determined by CLSI agar dilution, but with varied inocula. Mutant selection was investigated in single- and multi-step procedures. Results: MICs for methicillin-resistant Staphylococcus aureus (MRSA) were 0.5-2 mg/L, compared with 0.12-0.25 mg/L for methicillin-susceptible S. aureus; corresponding values for coagulase-negative staphylococci were 0.25-2 and 0.06-0.12 mg/L, respectively. Even with 2% NaCl added, all MRSA were susceptible at 2 mg/L. MICs for Enterococcus faecalis were from 0.25 to 8 mg/L; E. faecium was resistant. MICs for Escherichia coli, Klebsiella spp., Morganella morganii and Proteeae without acquired resistance were 0.06-0.5 mg/L versus 0.12-1 mg/L for Enterobacter, Serratia and Citrobacter spp. and 2-8 mg/L for Acinetobacter spp. MICs rose to 1-2 mg/L for many Enterobacteriaceae with classical TEM beta-lactamases, and were much higher for those with extended-spectrum beta-lactamases (ESBLs), hyperproduced AmpC or K1 enzymes. MICs for strains with classical TEM/SHV beta-lactamases rose if the inoculum was increased to 10(6) cfu/spot; this effect was even more marked for those with ESBLs. Resistance due to Class A beta-lactamases was reversed by clavulanate. Geometric mean MICs were 0.005, 0.05 and 0.09 mg/L for penicillin-susceptible, -intermediate and -resistant Streptococcus pneumoniae strains, respectively-lower than for any comparator beta-lactam. Haemophilus influenzae and Moraxella catarrhalis were very susceptible, although with marginally raised MICs for beta-lactamase-positive Moraxella strains and for haemophili with chromosomal ampicillin resistance. Ceftaroline selected AmpC-derepressed Enterobacter mutants similarly to cefotaxime in single-step experiments; in multi-step procedures it selected ESBL variants of blaTEM in E. coli. Resistance selection was not seen with S. aureus, H. influenzae or pneumococci. Conclusions: Ceftaroline has impressive anti-MRSA and anti-pneumococcal activity. Slight lability to classical TEM and SHV beta-lactamases is exceptional for an oxyimino-cephalosporin, but was reversible with clavulanate, as was the greater resistance mediated by ESBLs. Resistance selection occurred with Enterobacteriaceae, not MRSA.
TAK-599, a novel N-phosphono type prodrug of anti-MRSA cephalosporin T-91825: synthesis, physicochemical and pharmacological properties
Bioorg Med Chem 2003 May 29;11(11):2427-37.PMID:12735989DOI:10.1016/s0968-0896(03)00126-3.
Crystalline 1 (TAK-599) is a novel N-phosphono prodrug of anti-methicillin-resistant Staphylococcus aureus (MRSA) cephalosporin 2a (T-91825) that has high affinity for penicillin-binding protein (PBP) 2' (IC(50); 0.90 microg/mL) and shows potent in vitro anti-MRSA activity (MIC against MRSA N133; 1.56 microg/mL), comparable to that of vancomycin (1.56 microg/mL). Although 2a had insufficient water solubility (2.3 mg/mL) for parenteral administration, 1 showed excellent water solubility (>100 mg/mL, pH 7) as well as good chemical stability in the solid state and solution. In pharmacokinetic studies, when 1 was administered intravenously to rats and monkeys, it was rapidly converted into 2a in the blood. These results show that 1 (TAK-599) is a highly promising parenteral cephalosporin targeted for MRSA infection.
Ceftaroline fosamil: a cephalosporin with activity against methicillin-resistant Staphylococcus aureus
Clin Ther 2012 Apr;34(4):743-65.PMID:22444785DOI:10.1016/j.clinthera.2012.02.025.
Background: Ceftaroline is a cephalosporin with expanded gram-positive activity recently approved for clinical uses by the US Food and Drug Administration. Objective: This article provides an overview of the in vitro and in vivo activities, mechanism of action, pharmacologic and pharmacokinetic properties, clinical efficacy, and tolerability of ceftaroline. Methods: Relevant information was identified through a search of PubMed (1990-April 2011), EMBASE (1990-April 2011), International Pharmaceutical Abstracts (1970-April 2011), and Google Scholar using the key words ceftaroline, PPI-0903, PPI-0903M, T-91825, and TAK-599. A review of the reference lists of identified articles, a search of the US Food and Drug Administration Web site, and posters and abstracts from scientific meetings yielded additional publications. Results: In vitro, ceftaroline exhibits activity against most aerobic gram-positive isolates, common aerobic gram-negative respiratory pathogens, and some gram-positive anaerobes. The MIC range for most Staphylococcus aureus isolates, including vancomycin-resistant strains was between ≤0.008 and 4 μg/mL. In Phase III studies (CANVAS 1 and CANVAS 2), ceftaroline was found to be noninferior to vancomycin + aztreonam for the treatment of complicated skin and skin-structure infections, with a clinical cure rate of 91.6% among clinically evaluable patients (ceftaroline versus vancomycin + aztreonam: difference, -1.1; 95% CI, -4.2 to 2.0; P = NS). Ceftaroline's efficacy has also been assessed for the treatment of community-acquired pneumonia in 2 Phase III studies (FOCUS 1 and FOCUS 2) and was equivalent to ceftriaxone, with cure rates of 84.3% and 77.7%, respectively, among clinically evaluable patients in the combined analysis (ceftaroline versus ceftriaxone: difference, 6.7; 95% CI, 1.6 to 11.8). The recommended dosage for patients 18 years and older is 600 mg IV every 12 hours. Dosage adjustment is necessary in patients with renal impairment (creatinine clearance ≤50 mL/min). The pharmacokinetic properties of ceftaroline in patients with hepatic impairments are currently unavailable. Ceftaroline appeared to be well tolerated generally. The most frequently (>3%) reported adverse events were nausea, headaches, diarrhea, pruritus, rash, and insomnia; all were usually mild to moderate, self-limiting, and of little clinical significance. Conclusions: Ceftaroline is a cephalosporin with broad gram-positive activity, including Methicillin-resistant S aureus and vancomycin-resistant S aureus. Its gram-negative activity includes common respiratory pathogens and members of the Enterobacteriaceae. Clinical trials have reported that ceftaroline was noninferior to ceftriaxone, and vancomycin + aztreonam for the treatment of community-acquired pneumonia and complicated skin and skin-structure infections, respectively.
Stability and stabilization studies of TAK-599 (Ceftaroline Fosamil), a novel N-phosphono type prodrug of anti-methicillin resistant Staphylococcus aureus cephalosporin T-91825
Chem Pharm Bull (Tokyo) 2008 Oct;56(10):1406-11.PMID:18827379DOI:10.1248/cpb.56.1406.
TAK-599 (known as ceftaroline fosamil) is a novel N-phosphono type prodrug of a cephalosporin compound, T-91825, that exhibits strong activity against methicillin resistant Staphylococcus aureus (MRSA). The stability and stabilization of TAK-599 were investigated by kinetic analysis focused on crystallinity and moisture content. Initially it was planned to develop TAK-599 as an injectable formulation using the amorphous solid powder prepared by lyophilization. However, amorphous of TAK-599 free form was found to be chemically unstable even when stored at 8 degrees C, and thus development was focused on the crystalline material. After exhaustive screening of crystallization condition, the monoacetic acid solvate was found to yield TAK-599 in a crystalline form. Physicochemical properties were studied to identify the key factors affecting the stabilization of TAK-599 in order to improve long-term stability, and the results indicated that the crystallinity of TAK-599 correlated with stability. Furthermore, moisture content was also identified in our studies as an important factor in stabilizing TAK-599. TAK-599 containing about 3% moisture was found to be the most stable form. It was concluded that both sufficient crystallinity and strict moisture control of TAK-599 were essential to maintain long-term stability at 25 degrees C.