Streptonigrin (Bruneomycin)
(Synonyms: 棕霉素,Bruneomycin) 目录号 : GC32303
A phenylpyridylquinoline with diverse biological activities
Cas No.:3930-19-6
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
Streptonigrin is a phenylpyridylquinoline originally isolated from S. flocculus with diverse biological activities.1,2,3,4,5,6 Streptonigrin (2.5-12.5 μM) induces DNA cleavage by calf thymus topoisomerase II in a concentration-dependent manner.1 It induces phage production in S. typhimurium when used at concentrations ranging from 1 to 10 μg/ml.2 Streptonigrin (10 μg/ml) inhibits DNA synthesis in and reduces survival of S. typhimurium bacteria. Streptonigrin is bactericidal against E. coli in an iron-dependent manner, an effect that is blocked by the iron chelators deferoxamine and orthophenanthroline.3 Streptonigrin (40 nM) is cytotoxic to human HT-29 colon carcinoma cells but not to BE colon carcinoma cells in which NAD(P)H:quinone oxidoreductase is not expressed.4 Streptonigrin (0.001-0.1 μg/ml) inhibits mitosis and induces chromatin breaks in human leukocytes in a concentration-dependent manner.5 In vivo, streptonigrin (0.05 mg/kg, i.p.) increases the mean survival time in rats infected with Rauscher virus.6
1.Yamashita, Y., Kawada, S., Fujii, N., et al.Induction of mammalian DNA topoisomerase II dependent DNA cleavage by antitumor antibiotic streptonigrinCancer Res.50(18)5841-5844(1990) 2.Levine, M., and Borthwick, M.The action of streptonigrin on bacterial DNA metabolism and on induction of phage production in lysogenic bacteriaVirology21(4)568-574(1963) 3.Yeowell, H.N., and White, J.R.Iron requirement in the bactericidal mechanism of streptonigrinAntimicrob. Agents Chemother.22(6)961-968(1982) 4.Beall, H.D., Liu, Y., Siegel, D., et al.Role of NAD(P)H:quinone oxidoreductase (DT-diaphorase) in cytotoxicity and induction of DNA damage by streptonigrinBiochem. Pharmacol.51(5)645-652(1996) 5.Cohen, M.M., Shaw, M.W., and Craig, A.P.The effects of streptonigrin on cultured human leukocytesProc. Natl. Acad. Sci. USA50(1)16-24(1963) 6.McBride, T.J., Oleson, J.J., and Woolf, D.The activity of streptonigrin against the Rauscher murine leukemia virus in vivoCancer Res.26(4)727-732(1966)
| Cas No. | 3930-19-6 | SDF | |
| 别名 | 棕霉素,Bruneomycin | ||
| Canonical SMILES | O=C(C1=NC(C2=NC3=C(C(C(OC)=C(N)C3=O)=O)C=C2)=C(N)C(C4=CC=C(OC)C(OC)=C4O)=C1C)O | ||
| 分子式 | C25H22N4O8 | 分子量 | 506.46 |
| 溶解度 | Chloroform:Methanol (1:1): 2 mg/ml | 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 | 1.9745 mL | 9.8724 mL | 19.7449 mL |
| 5 mM | 0.3949 mL | 1.9745 mL | 3.949 mL |
| 10 mM | 0.1974 mL | 0.9872 mL | 1.9745 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。
Streptonigrin Mitigates Lung Cancer-induced Cachexia by Suppressing TCF4/TWIST1-induced PTHLH Expression
Anticancer Res 2023 Mar;43(3):1149-1157.PMID:36854496DOI:10.21873/anticanres.16260.
Background/aim: Cachexia - a wasting disorder of adipose and skeletal muscle tissue - is the most common driver of poor prognosis in patients with advanced lung cancer. Parathyroid hormone-like hormone (PTHLH) is potentially a critical factor in cancer-associated cachexia. We previously showed that Streptonigrin - an aminoquinone with antitumor effects - inhibited the interaction between TCF4 and TWIST1. This study aimed to determine the anti-cachectic performance of Streptonigrin in lung cancer. Materials and methods: We assessed the effect of Streptonigrin on the interaction of TCF4 and TWIST1 using co-immunoprecipitation and a mammalian-two hybrid luciferase assay, which was confirmed by an in vitro GST pull-down assay using recombinant bHLH domain-containing TCF4 and TWIST1. We assessed the anti-cachectic effect of Streptonigrin in vivo using an LLC1 cell-induced tumour-bearing mouse model. Changes in the degree of skeletal muscle and adipose tissue wasting were determined by measuring the weights of gastrocnemius and epidydimal white adipose tissue. Results: Streptonigrin was found to inhibit the interaction of TCF4 with TWIST1 in a dose-dependent manner. The in vitro GST pull-down assay revealed that Streptonigrin directly inhibited the interaction between TCF4 and TWIST1. The expression of PTHLH mRNA, which is transcriptionally regulated by the TCF4/TWIST1 complex in response to TGF-尾1 signalling, was decreased in streptonigrin-treated lung cancer cells. Streptonigrin significantly decreased the expression of proteolysis-related genes in skeletal muscle and browning-related genes in white adipose tissues of LLC1-induced tumour-bearing mice. Conclusion: Streptonigrin exerts potent therapeutic effects on lung cancer-induced cachexia by suppressing TCF4/TWIST1-mediated PTHLH expression.
Streptonigrin at low concentration promotes heterochromatin formation
Sci Rep 2020 Feb 26;10(1):3478.PMID:32103104DOI:10.1038/s41598-020-60469-6.
Heterochromatin is essential for regulating global gene transcription and protecting genome stability, and may play a role in tumor suppression. Drugs promoting heterochromatin are potential cancer therapeutics but very few are known. In order to identify drugs that can promote heterochromatin, we used a cell-based method and screened NCI drug libraries consisting of oncology drugs and natural compounds. Since heterochromatin is originally defined as intensely stained chromatin in the nucleus, we estimated heterochromatin contents of cells treated with different drugs by quantifying the fluorescence intensity of nuclei stained with Hoechst DNA dye. We used HeLa cells and screened 231 FDA-approved oncology and natural substance drugs included in two NCI drug libraries representing a variety of chemical structures. Among these drugs, Streptonigrin most prominently caused an increase in Hoechst-stained nuclear fluorescence intensity. We further show that Streptonigrin treated cells exhibit compacted DNA foci in the nucleus that co-localize with Heterochromatin Protein 1 alpha (HP1伪), and exhibit an increase in total levels of the heterochromatin mark, H3K9me3. Interestingly, we found that Streptonigrin promotes heterochromatin at a concentration as low as one nanomolar, and at this concentration there were no detectable effects on cell proliferation or viability. Finally, in line with a previous report, we found that Streptonigrin inhibits STAT3 phosphorylation, raising the possibility that non-canonical STAT function may contribute to the effects of Streptonigrin on heterochromatin. These results suggest that, at low concentrations, Streptonigrin may primarily enhance heterochromatin formation with little toxic effects on cells, and therefore might be a good candidate for epigenetic cancer therapy.
Genotoxicity of Streptonigrin: a review
Mutat Res 2001 Mar;488(1):25-37.PMID:11223403DOI:10.1016/s1383-5742(00)00062-4.
Streptonigrin (SN, CAS no. 3930-19-6) is an aminoquinone antitumor antibiotic isolated from cultures of Streptomyces flocculus. This compound is a member of a group of antitumor agents which possess the aminoquinone moiety and that includes also mitomycin C, porfiromycin, actinomycin, rifamycin and geldanamycin. Because of the potential use of SN in clinical chemotherapy, the study of its genotoxicity has considerable practical significance.SN inhibits the synthesis of DNA and RNA, causes DNA strand breaks after reduction with NADH, induces unscheduled DNA synthesis and DNA adducts and inhibits topoisomerase II. At the chromosome level, this antibiotic causes chromosome damage and increases the frequency of sister-chromatid exchanges.SN cleaves DNA in cell-free systems by a mechanism that involves complexing with metal ions and autoxidation of the quinone moiety to semiquinone in the presence of NADH with production of oxygen-derived reactive species. Recent evidence strongly suggests that the clastogenic action of this compound is partially mediated by free radicals. The present review aims at summarizing past and current knowledge concerning the genotoxic effects of SN.
Methyl 1-(7-acetamido-5,8-dimeth-oxy-quinolin-2-yl)-4-methyl-尾-carboline-3-carboxyl-ate
Acta Crystallogr Sect E Struct Rep Online 2011 Jun 1;67(Pt 6):o1497-8.PMID:21754865DOI:10.1107/S1600536811018794.
The title compound, C(27)H(24)N(4)O(5), is an inter-mediate in the synthesis of lavendamycin via a ruthenium-catalysed [2 + 2 + 2] cyclo-addition. An intra-molecular hydrogen-bond bridge from the carboline to the quinoline stabilizes a highly planar geometry [maximum deviation = 0.065 (6) 脜] for the two rigid units. This hydrogen-bond-stabilized coplanarity has a very close analogy in the structure of the anti-tumor anti-biotic Streptonigrin in the solid state and in solution. Inter-molecular hydrogen-bond bridges of amides groups along the a axis and 蟺-蟺 stacking inter-actions [centroid-centroid distance = 3.665 (9) 脜] connect mol-ecules arranged in a parallel manner.
A novel Streptonigrin type alkaloid from the Streptomyces flocculus CGMCC 4.1223 mutant 螖 stnA/Q2
Nat Prod Res 2022 Jul;36(13):3337-3345.PMID:33280413DOI:10.1080/14786419.2020.1856840.
Streptonigrin (STN) is a highly functionalized aminoquinone alkaloid with broad and potent antitumor activities. Previously, the biosynthetic gene cluster of STN was identified in Streptomyces flocculus CGMCC 4.1223, revealing an 伪/尾-hydrolase (StnA) and a methyltransferase (StnQ2). In this work, a double mutant 螖stnA/Q2 was constructed by genetic manipulation and produced a novel derivative of STN, named as streptonigramide. Structure of streptonigramide was established by spectroscopic analyses. Its biosynthetic pathway has been proposed as well.