Rifalazil
(Synonyms: 利福拉齐; KRM-1648; ABI-1648) 目录号 : GC61246
Rifalazil(ABI-1648;KRM-1648)是利福霉素衍生物，可抑制细菌依赖DNA的RNA聚合酶(RNApolymerase)并阻断RNA聚合酶中的β亚基从而杀死细菌感染的细胞。Rifalazil(ABI-1648;KRM-1648)是一种抗生素(antibiotic)，对分枝杆菌，革兰氏阳性细菌，幽门螺杆菌，肺炎衣原体和沙眼衣原体有抑制作用，其MIC值在0.00025至0.0025μg/ml之间。Rifalazil(ABI-1648;KRM-1648)有潜力用于衣原体感染，梭菌相关性腹泻菌感染 (CDAD)和结核病(TB)研究的相关研究。
Cas No.:129791-92-0
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
Rifalazil (KRM-1648; ABI-1648), a rifamycin derivative, inhibits the bacterial DNA-dependent RNA polymerase and kills bacterial cells by blocking off the β-subunit in RNA polymerase[1]. Rifalazil (KRM-1648; ABI-1648) is an antibiotic, exhibits high potency against mycobacteria, gram-positive bacteria, Helicobacter pylori, C. pneumoniae and C. trachomatis with MIC values from 0.00025 to 0.0025 μg/ml[3]. Rifalazil (KRM-1648; ABI-1648) has the potential for the treatment of Chlamydia infection, Clostridium difficile associated diarrhea (CDAD), and tuberculosis (TB)[2].
Rifalazil exhibits antimicrobal activity against Gram-positive enteric bacteria, inhibits Clostridium difficile, Clostridium perfringens, Bacteroides fragilis with MIC50 value of 0.0015, 0.0039, 0.0313 µg/ml, respectively[3].Rifalazil exhibits antimicrobal activity against Gram-negative enteric bacteria, inhibits Escherichia coli and Klebsiella pneumoniae with MIC50 value of 16 and 16 µg/ml, respectively[3].Rifalazil exhibits antimicrobal activity against non-enteric Gram-positive bacteria, inhibits Methicillin-susceptible Staphylococcus aureus, Methicillin-resistant S. aureus, Methicillin- and quinolone-resistant S. aureus, Staphylococcus epidermidis, Streptococcus pyogenes, Streptococcus pneumoniae with MIC50 value of 0.0078, 0.0078, 0.0078, 0.0078, 0.0002, 0.0001 µg/ml, respectively[3].Rifalazil exhibits antimicrobal activity against Helicobacter pylori, Chlamydia pneumoniae and Chlamydia trachomatis with MIC50 value of 0.004, 0.000125 and 0.00025 µg/ml, respectively[3].
Rifalazil (oral gavage; 20, 25, and 150 mg/kg; 6-8 weeks) combines with isoniazid (INH) for 6 weeks or greater significantly reduced the number of mice per group in which M. tuberculosis is detected in both spleens and lungs compared to the reductions for the early and late controls. And the addition of Pyrazinamide (PZA) does not significantly improve RLZ-INH therapy at any time point[2]. Animal Model: Female CD-1 mice infected with 5.2 × 107 viable mycobacteria[2]
[1]. Suchland RJ, et al. Rifalazil pretreatment of mammalian cell cultures prevents subsequent Chlamydia infection.Antimicrob Agents Chemother. 2006 Feb;50(2):439-44. [2]. Shoen CM, et al. Evaluation of rifalazil in long-term treatment regimens for tuberculosis in mice.Antimicrob Agents Chemother. 2000 Jun;44(6):1458-62. [3]. Rothstein DM, et al. Development potential of rifalazil.Expert Opin Investig Drugs. 2003 Feb;12(2):255-71.
| Cas No. | 129791-92-0 | SDF | |
| 别名 | 利福拉齐; KRM-1648; ABI-1648 | ||
| Canonical SMILES | CC(C)CN(CC1)CCN1C2=CC(O3)=C(C(O)=C2)N=C(C3=C(NC(/C(C)=C\C=C\[C@@H]([C@H](O)[C@@H](C)[C@@H](O)[C@@H](C)[C@@H]([C@@H]([C@H](/C=C/O[C@@]4(C)O5)OC)C)OC(C)=O)C)=O)C6=O)C7=C6C(O)=C(C)C5=C7C4=O | ||
| 分子式 | C51H64N4O13 | 分子量 | 941.07 |
| 溶解度 | DMSO: 8.33 mg/mL (8.85 mM) | 储存条件 | 4°C, away from moisture |
| 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 | 1.0626 mL | 5.3131 mL | 10.6262 mL |
| 5 mM | 0.2125 mL | 1.0626 mL | 2.1252 mL |
| 10 mM | 0.1063 mL | 0.5313 mL | 1.0626 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。
Rifalazil and other benzoxazinorifamycins in the treatment of chlamydia-based persistent infections
Arch Pharm (Weinheim) 2007 Oct;340(10):517-29.PMID:17912677DOI:10.1002/ardp.200700080.
Rifalazil is a benzoxazinorifamycin which inhibits bacterial DNA-dependent RNA polymerase. The benzoxazine ring endows benzoxazinorifamycins with unique physical and chemical characteristics which favor the use of Rifalazil and derivatives in treating diseases caused by the obligate intracellular pathogens of the genus chlamydia. Minimal inhibitory concentrations of benzoxazinorifamycins against chlamydia are in the pg/mL range. These compounds have potential as monotherapeutic agents to treat chlamydia-associated disease because they retain activity against chlamydia strains resistant to currently approved rifamycins such as rifampin. A pivotal clinical trial with Rifalazil has been initiated for the treatment of peripheral arterial disease. The rationale for this innovative use of Rifalazil, including the association of C. pneumoniae in atherosclerotic plaque formation, as well as Rifalazil's potency and efficacy against chlamydia in both preclinical and clinical studies, is discussed. Other benzoxazino derivatives may have utility as stand-alone topical antibacterials or combination antibacterials to treat serious Gram-positive infections. None of the benzoxazinorifamycins examined to date induce the cytochrome P450 3A4 enzyme. This is in contrast to currently approved rifamycins which are strong inducers of P450 enzymes, resulting in drug-drug interactions that limit the clinical utility of this drug class.
Development potential of Rifalazil and other benzoxazinorifamycins
Expert Opin Investig Drugs 2006 Jun;15(6):603-23.PMID:16732714DOI:10.1517/13543784.15.6.603.
Rifalazil and other benzoxazinorifamycins (new chemical entities [NCEs]) are rifamycins that contain a distinct planar benzoxazine ring. Rifalazil has excellent antibacterial activity, high intracellular levels and high tissue penetration, which are attributes that favour its use in treating diseases caused by the obligate intracellular pathogens of the genus Chlamydia. Recent studies have shown that Rifalazil has efficacy in the treatment of human sexually transmitted disease caused by Chlamydia trachomatis. The extraordinary potency of Rifalazil and other NCEs, such as ABI-0043, extends to the related microorganism, C. pneumoniae, a respiratory pathogen that can disseminate and persist chronically in the vasculature, resulting in increased plaque formation in animal studies. A pivotal clinical trial with Rifalazil has been initiated for the treatment of peripheral arterial disease. Other opportunities include gastric ulcer disease caused by Helicobacter pylori and antibiotic-associated colitis caused by infection with Clostridium difficile in the colon. The NCEs could prove to be valuable as follow-on compounds in these indications, as rifampin replacements in antibacterial combination therapy or as stand-alone topical antibacterials (e.g., to treat acne). Neither Rifalazil nor NCEs appear to induce the cytochrome P450 3A4, an attribute of rifampin that can result in adverse events due to drug-drug interactions.
Development potential of Rifalazil
Expert Opin Investig Drugs 2003 Feb;12(2):255-71.PMID:12556219DOI:10.1517/13543784.12.2.255.
Rifalazil represents a new generation of ansamycins that contain a unique four-ring structure. Originally Rifalazil was developed as a therapeutic agent to replace rifampin as part of a multiple drug regimen in the treatment of tuberculosis. As a result of its superior antimicrobial activity and high intracellular levels, Rifalazil has potential to treat indications caused by the intracellular pathogen, Chlamydia trachomatis, which causes non-gonococcal urethritis and cervicitis, often leading to pelvic inflammatory disease. Rifalazil also has potential to treat the related microorganism, Chlamydia pneumoniae, which may be involved in chronic inflammatory processes thought to be partly responsible for atherosclerosis. Due to its favourable antimicrobial spectrum and other positive attributes, Rifalazil may also prove valuable in the treatment of gastric ulcer disease, caused by Helicobacter pylori, and antibiotic-associated colitis, the result of toxin production following the growth of Clostridium difficile in the colon. The potential value of Rifalazil in the treatment of these indications will be assessed in human clinical trials.
A Comparative Insight on the Newly Emerging Rifamycins: Rifametane, Rifalazil, TNP-2092 and TNP-2198
Curr Med Chem 2022;29(16):2846-2862.PMID:34365945DOI:10.2174/0929867328666210806114949.
Rifamycins are considered a milestone for tuberculosis (TB) treatment because of their proficient sterilizing ability. Currently, available TB treatments are complicated and need a long duration, which ultimately leads to failure of patient compliance. Some new rifamycin derivatives, i.e., rifametane, TNP-2092 (rifamycin-quinolizinonehybrid), and TNP-2198 (rifamycin-nitromidazole hybrid) are under clinical trials, which are attempting to overcome the problems associated with TB treatment. The undertaken review is intended to compare the pharmacokinetics, pharmacodynamics and safety profiles of these rifamycins, including Rifalazil, another derivative terminated in phase II trials, and already approved rifamycins. The emerging resistance of microbes is an imperative consideration associated with antibiotics. Resistance development potential of microbial strains against rifamycins and an overview of chemistry, as well as structure-activity relationship (SAR) of rifamycins, are briefly described. Moreover, issues associated with rifamycins are discussed as well. We expect that newly emerging rifamycins shall appear as potential tools for TB treatment in the near future.
Rifalazil(Kaneka corp)
IDrugs 1998 Sep;1(5):599-604.PMID:18465600doi
Rifalazil is a rifamycin derivative from Kaneka that is in phase II clinical trials for the treatment of Mycobacterium tuberculosis (M tuberculosis; TB) and AIDS-associated Mycobacterium avium complex (MAC) infections [108254, 165543]. PathoGenesis has licensed the compound exclusively from Kaneka for its development and marketing in the US and Mexico, and is conducting phase I clinical trials in the US for both indications [223964]. In October 1997, Pathogenesis initiated a phase II trial in Brazil in which 60 pulmonary TB patients were enrolled. Fourteen-day dosing regimens in four groups will compare combinations of Rifalazil and isoniazid with isoniazid alone or isoniazid plus rifampin. The early bactericidal activity of Rifalazil will be evaluated, and results are expected at the end of 1998 [266596,292118]. In phase I clinical trials, low but potentially therapeu-tically useful doses (100 mg) have shown none of the side-effects seen with rifampin therapy. Rifalazil also has a longer half-life than rifampin (24 h compared to 2 to 3 h for rifampin). These trials were completed in 1996 [223964]. In preclinical in vitro studies, Rifalazil was 30-fold more potent than rifampin against M tuberculosis and MAC, and has shown efficacy in animal models of tuberculosis and in disseminated MAC infections that have been predictive of clinical efficacy with other antibiotics [224163].The major metabolites, KRM-1671 and KRM-1690 are as active and slightly less active than the parent compound, respectively [187790]. In March 1998, PathoGenesis received a Small Business Innovation Research Grant from the National Institute of Allergy and Infectious Diseases to support antituberculosis research. The company has developed new techniques in automated combinatorial chemistry and microbiological drug susceptibility testing that will expedite its research [282227].