Coumermycin A1
(Synonyms: 香豆霉素) 目录号 : GC62908
Coumermycin A1 是一种 JAK2 信号激活剂。Coumermycin A1 抑制 DNA 旋转酶 (DNA Gyrase)，从而抑制细菌的细胞分裂。
Cas No.:4434-05-3
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
Coumermycin A1 is a JAK2 signal activator. Coumermycin A1 inhibits DNA Gyrase which thereby inhibits cell division in bacteria.
Coumermycin A1-induced-JAK2 signal activation increases the mRNA level of SCOS2, but reducea leptin receptor mRNA level[1].
[1]. Tiantian Zhang, et al. SOCS2 Inhibits Mitochondrial Fatty Acid Oxidation via Suppressing LepR/JAK2/AMPK Signaling Pathway in Mouse Adipocytes. Research Article.
| Cas No. | 4434-05-3 | SDF | |
| 别名 | 香豆霉素 | ||
| 分子式 | C55H59N5O20 | 分子量 | 1110.08 |
| 溶解度 | DMSO : 50 mg/mL (45.04 mM; Need ultrasonic and warming) | 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 | 0.9008 mL | 4.5042 mL | 9.0084 mL |
| 5 mM | 0.1802 mL | 0.9008 mL | 1.8017 mL |
| 10 mM | 0.0901 mL | 0.4504 mL | 0.9008 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。
Structural Basis for DNA Gyrase Interaction with Coumermycin A1
J Med Chem 2019 Apr 25;62(8):4225-4231.PMID:30920824DOI:10.1021/acs.jmedchem.8b01928.
Coumermycin A1 is a natural aminocoumarin that inhibits bacterial DNA gyrase, a member of the GHKL proteins superfamily. We report here the first cocrystal structures of gyrase B bound to Coumermycin A1, revealing that one Coumermycin A1 molecule traps simultaneously two ATP-binding sites. The inhibited dimers from different species adopt distinct sequence-dependent conformations, alternative to the ATP-bound form. These structures provide a basis for the rational development of Coumermycin A1 derivatives for antibiotherapy and biotechnology applications.
Coumermycin A1: A preferential inhibitor of replicative DNA synthesis in Escherichia coli. I. In vivo characterization
Biochemistry 1976 Aug 24;15(17):3769-77.PMID:782522DOI:10.1021/bi00662a020.
Coumermycin A1, an antibiotic related to novobiocin, inhibited nucleic acid synthesis in intact Escherichia coli with replication being slightly more sensitive to this drug than transcription. The ultraviolet-induced repair synthesis of DNA was only partially inhibited under conditions where replication was eliminated by Coumermycin A1. Inhibition of protein synthesis was a secondary effect. Coumermycin A1-resistant E. coli were isolated and the mutation was mapped near dnaA. Chromatography of crude protein extracts of sensitive and resistant bacteria on drug affinity columns implicated a soluble protein of approximately 37,000 molecular weight as the target site for Coumermycin A1. Depending on the medium used, this antibiotic had either a bacteriocidal or a bacteriostatic effect on E. coli. Results showed that the effect of Coumermycin A1 cannot be explained by the degradation of DNA under bacteriocidal growth conditions.
Treatment of Staphylococcus aureus endocarditis in rats with Coumermycin A1 and ciprofloxacin, alone or in combination
Antimicrob Agents Chemother 1987 Apr;31(4):539-43.PMID:3606060DOI:10.1128/AAC.31.4.539.
The efficacy of a 5-day treatment with Coumermycin A1 (hereafter referred to as coumermycin) (at three dosage regimens), with ciprofloxacin, or with coumermycin plus ciprofloxacin was tested in experimental aortic valve endocarditis induced in rats by a strain of methicillin-susceptible Staphylococcus aureus and was compared with the efficacy of a 5-day treatment with cloxacillin plus gentamicin. While coumermycin was far less effective than cloxacillin plus gentamicin in reducing the bacterial counts in vegetations (P less than 10(-8), ciprofloxacin was as effective as cloxacillin plus gentamicin. Coumermycin plus ciprofloxacin was less effective than ciprofloxacin alone (P = 0.01). For endocarditis induced by two additional methicillin-susceptible S. aureus strains, the high-dosage regimen of coumermycin (12 mg/kg every 12 h) had the same low efficacy. Coumermycin-resistant variants of S. aureus emerged in most of the vegetations during coumermycin treatment. The ciprofloxacin susceptibility of S. aureus was unchanged during ciprofloxacin treatment. The addition of ciprofloxacin to coumermycin in the treatment did not prevent the emergence of coumermycin-resistant variants. Twelve additional S. aureus strains isolated from the blood of patients with endocarditis were tested in vitro against coumermycin with precautions to avoid carry-over of the antibiotic. Coumermycin exhibited a bacteriostatic activity at very low concentrations (MIC, less than 0.004 microgram/ml) but only a weak bactericidal activity (MBC for 90% of strains, 8 micrograms/ml), a finding contrasting with that of others. Furthermore, coumermycin-resistant mutants could be selected in vitro from the 15 S. aureus strains tested. These results indicated no evidence in vivo of a synergistic activity of coumermycin and ciprofloxacin. More importantly, these results suggested that coumermycin might not be adequate for the treatment of serious s. aureus infections in humans.
Coumermycin A1 inhibits growth and induces relaxation of supercoiled plasmids in Borrelia burgdorferi, the Lyme disease agent
Antimicrob Agents Chemother 1993 Jan;37(1):46-50.PMID:8381639DOI:10.1128/AAC.37.1.46.
Coumermycin A1 is an inhibitor of DNA gyrase, an enzyme that catalyzes supercoiling of DNA and is required for bacterial DNA replication. We have investigated the activity of this coumarin antibiotic on Borrelia burgdorferi, a spirochete and the causative agent of Lyme disease. B. burgdorferi was more susceptible than many other eubacteria to coumermycin as well as novobiocin, another coumarin antibiotic; this contrasted with its relative resistance to the DNA gyrase inhibitors nalidixic acid, oxolinic acid, and ciprofloxacin. Coumermycin at 0.2 micrograms/ml inhibited the growth of B. burgdorferi B31 in BSK II medium. A 100-fold-lower concentration induced the relaxation of two negatively supercoiled circular plasmids within 2 h. Plasmid supercoiling was restored within 2 h of removal of coumermycin. These results suggest that B. burgdorferi has a DNA gyrase and that this enzyme's activity is required for growth. Furthermore, structural analogs of coumermycin may be considered as treatments for Lyme disease.
In vitro activity of Coumermycin A1
Appl Microbiol 1969 Nov;18(5):869-73.PMID:4391844DOI:10.1128/am.18.5.869-873.1969.
The in vitro activity of coumermycin A(1) was compared with that of novobiocin, ampicillin, and minocycline. Coumermycin was found to be the most active antibiotic of the four against Staphylococcus aureus. It was about 50 times more active than novobiocin or minocycline against the strains tested. Coumermycin also showed good activity against group A streptococci and pneumococci, moderate activity against Escherichia coli, indole-positive Proteus species, and Pseudomonas aeruginosa, and poor activity against Klebsiella-Enterobacter and enterococci. Against P. mirabilis, however, coumermycin activity was almost equal to that of ampicillin. The new antibiotic was further found to be greatly reduced in activity in the presence of plasma, but its minimal inhibitory concentration was not greatly affected by inoculum size. Coumermycin was found to be bacteriostatic in its action, and resistance to it developed slowly. Also, cross-resistance was present with novobiocin but absent with ampicillin or minocycline.