Bleomycin Sulfate
(Synonyms: 硫酸博来霉素) 目录号 : GC15819
博来霉素由链霉菌产生。
Cas No.:9041-93-4
Sample solution is provided at 25 µL, 10mM.
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Related Biological Data
Gracillin alleviates collagen deposition and pulmonary function in mice with BLM-induced PF. (A) HE staining of lung sections, 40 × magnification, scale bar: 250 μm; 200 × magnification, scale bar: 50 μm.
PF was induced in model mice via a single intratracheal BLM (3 mg/kg) (GLPBIO) instillation.
Journal of Ethnopharmacology (2023): 116704. PMID: 37257706 IF: 5.3999 -
Related Biological Data
Baicalin mitigated cell apoptosis in both bleomycin-induced pulmonary fibrosis and bleomycin-treated MLE-12; this effect was impeded by 5-HD. (C) Cell apoptosis was examined through flow cytometry.
In vitro, MLE-12 cells were treated with BLM (35 μM) (GLPBIO) for 24 h to induce cell injury.
Toxicology (2023): 153638. PMID: 37783230 IF: 4.5003 -
Related Biological Data
hESC-MSC-Exos mitigate Pt- and BLM-induced γH2AX protein level increase. (C) and (D): Quantification results of γH2AX fluorescence intensity from (A) and (B), respectively.
Consistent with previous reports, after HeLa cells were treated with 1 μMol/L Pt or 10 μMol/L BLM(GLPBIO) for 24 h, the intracellular ROS level increased robustly in comparison with the untreated group as measured by DCFH staining.
Mutat Res-Gen Tox En (2023): 503651. PMID: 37491116 IF: 1.9 -
Related Biological Data
6-Gingerol improves the survival rate of bleomycin-induced mice and reduces lung pathology. (B) The changes of lung pathology in each group were observed by H&E staining.
The mice were randomly divided into four groups: control,BLM, BLM + 6-gingerol 100 mg/kg, BLM + 6-gingerol 250 mg/kg. BLM group: for the induction of fibrosis, BLM (purity > 98.00%, GlpBio, United States) was dissolved in 50 μL sterile PBS, and mice were intratracheally administered (2 mg/kg body weight) with a single dose of BLM.
Allergol Immunopath 50.2 (2022): 104-114. PMID: 35257553 IF: 1.667
Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
| Cell experiment [1]: | |
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Cell lines |
Hela cells |
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Preparation Method |
HeLa cells, labelled with 3H~thymidine (0.05 pic/ml, 1,850 mc/mM) for 20 hours, |
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Reaction Conditions |
Cells were incubated with bleomycin A2 (8 or 40 μg/ml) for 6 hours at 37°C. |
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Applications |
Bleomycin can cause the single-strand scission. The sulfhydryl compound is necessary for bleomycin A2 to cause scission in DNA strand as in the case of decreasing Tm of DNA. Unless EDTA was added to the cell suspension, more marked scission of DNA was demonstrated. The enhancement of DNA degradation seemed to occur during the extraction procedure. |
| Animal experiment [2]: | |
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Animal models |
D1CC×D1BC tg mice，bred on a DBA/1J background |
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Preparation Method |
Bleomycin was mixed with an equal amount of microbubbles (Ultrasound Contrast Agent SV-25) and administered via the i.t. route by a spray nebulizer (40 μl/mouse, 1.28 mg/kg body weight) before sonoporation on the chest by 1.0 W/cm2 for 1 min (Sonitron GTS Sonoporation System). Mice were anesthetized with isoflurane and the chest hair was shaved for sonoporation. |
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Dosage form |
0.512 mg/ml in normal saline |
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Applications |
Bleomycin is most commonly used to develop pulmonary fibrosis in animal models. In animal models, administration of single or multiple doses of bleomycin by either intra-tracheal (i.t.) instillation, osmotic pump, intravenous route, or intranasal delivery induces pulmonary fibrosis, results in significant dose-dependent mortality. |
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References: [1]. Suzuki H, et al. On the mechanism of action of bleomycin: scission of DNA strands in vitro and in vivo. J Antibiot (Tokyo). 1969 Sep;22(9):446-8. [2]. Yoko Miura, et al. Bimodal fibrosis in a novel mouse model of bleomycin-induced usual interstitial pneumonia. Life Sci Alliance. 2022 Jan; 5(1): e202101059. |
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Bleomycin is produced by Streptomyces verticillis. The Bleomycin molecule has two main structural components; a bithiazole component which partially intercalates into the DNA helix, parting the strands, as well as pyrimidine and imidazole structures, which bind iron and oxygen forming an activated complex capable of releasing damaging oxidants in close proximity to the polynucleotide chains of DNA. This may lead to chain scission or structural modifications leading to release of free bases or their propenal derivatives. It has potent tumor killing properties which have gained it an critical role in cancer chemotherapy. It causes little marrow suppression, but the major adverse is pulmonary toxicity effect.[1]
In vitro, Bleomycin reacts with DNA which has previously been treated with a sulfhydryl compound, and cause a decrease in its melting temperature (Tm). In the reactions in vitro, strand scission in DNA has been confirmed which indicate that in the presence of a sulfhydryl compound in vitro, Bleomycin binds to DNA, and causes single-strand scission. The scission of DNA may be the cause of the inhibition of thymidine incorporation into DNA of growing cells and the inhibition of cell division. [2]
In vivo study demonstrated that Bleomycin-induced pulmonary toxicity and fibrosis could be significantly affected by Soluble epoxide hydrolase (sEH) inhibitors AUDA. In vivo, AUDA significantly improved Bleomycin -induced decline in lung function and body weight, and inhibited inflammatory cell accumulation and the mRNA and protein expression of interleukin (IL)-1β, TGF-β1, and matrix metalloproteinase 9 (MMP-9) in lung tissue. [3]
References:
[1]. John H. et al. Mechanisms of Bleomycin-induced lung damage. Arch Toxicol (1991) 65:81-94.
[2]. Suzuki H, et al. On the mechanism of action of Bleomycin: scission of DNA strands in vitro and in vivo. J Antibiot (Tokyo). 1969 Sep;22(9):446-8.
[3]. Xin-wei D, et al. Soluble epoxide hydrolase inhibitor AUDA decreases Bleomycin-induced pulmonary toxicity in mice by inhibiting the p38/Smad3 pathways. Toxicology 389 (2017) 31–41.
博来霉素由链霉菌产生。博来霉素分子有两个主要结构成分；一种双噻唑成分,部分嵌入 DNA 螺旋结构,分开链,以及嘧啶和咪唑结构,它们结合铁和氧形成活化复合物,能够在靠近 DNA 多核苷酸链的地方释放有害氧化剂。这可能会导致断链或结构修饰,从而导致游离碱基或其丙烯醛衍生物的释放。它具有强大的肿瘤杀伤特性,这使其在癌症化学疗法中发挥了关键作用。它几乎没有骨髓抑制作用,但主要的副作用是肺毒性作用。[1]
在体外,博来霉素与先前用巯基化合物处理过的 DNA 发生反应,导致其熔解温度 (Tm) 降低。在体外反应中,已证实 DNA 链断裂,这表明在体外存在巯基化合物的情况下,博来霉素与 DNA 结合,并导致单链断裂。 DNA 的断裂可能是抑制胸苷掺入生长细胞的 DNA 和抑制细胞分裂的原因。 [2]
体内研究表明,可溶性环氧化物水解酶 (sEH) 抑制剂 AUDA 可显着影响博来霉素诱导的肺毒性和纤维化。在体内,AUDA 显着改善博来霉素引起的肺功能和体重下降,并抑制炎症细胞积聚和白细胞介素 (IL)-1β、TGF-β1 和基质金属蛋白酶 9 (MMP-9) 的 mRNA 和蛋白表达肺组织。 [3]
| Cas No. | 9041-93-4 | SDF | |
| 别名 | 硫酸博来霉素 | ||
| 化学名 | 3-[[2-[2-[2-[[(2R,3R)-2-[[(2R,3R,4S)-4-[[(2S)-2-[[6-amino-2-[(1S)-3-amino-1-[[(2R)-2,3-diamino-3-oxopropyl]amino]-3-oxopropyl]-5-methylpyrimidine-4-carbonyl]amino]-3-[(2S,3R,4R,5R,6R)-3-[(2R,3S,4S,5R,6R)-4-carbamoyloxy-3,5-dihydroxy-6-(hydroxymethyl)oxan- | ||
| Canonical SMILES | CC1=C(N=C(N=C1N)C(CC(=O)N)NCC(C(=O)N)N)C(=O)NC(C(C2=CN=CN2)OC3C(C(C(C(O3)CO)O)O)OC4C(C(C(C(O4)CO)O)OC4C(C(C(C(O4)CO)O)OC(=O)N)O)C(=O)NC(C)C(C(C)C(=O)NC(C(C)O)C(=O)NCCC5=NC(=CS5)C6=NC(=CS6)C(=O)NCCC[S+](C)C)O.OS(=O)(=O)[O-] | ||
| 分子式 | C55H85N17O25S4 | 分子量 | 1512.6 |
| 溶解度 | ≥ 125 mg/mL in DMSO with gentle warming, ≥ 151.3 mg/mL in Water with ultrasonic, <7.45 mg/mL in EtOH | 储存条件 | Store at -20°C,sealed storage, 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 | 0.6611 mL | 3.3056 mL | 6.6111 mL |
| 5 mM | 0.1322 mL | 0.6611 mL | 1.3222 mL |
| 10 mM | 0.0661 mL | 0.3306 mL | 0.6611 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。
Heparan Sulfate and Chondroitin Sulfate Glycosaminoglycans Are Targeted by Bleomycin in Cancer Cells
Background/aims: Bleomycin is a clinically used anti-cancer drug that produces DNA breaks once inside of cells. However, bleomycin is a positively charged molecule and cannot get inside of cells by free diffusion. We previously reported that the cell surface negatively charged glycosaminoglycans (GAGs) may be involved in the cellular uptake of bleomycin. We also observed that a class of positively charged small molecules has Golgi localization once inside of the cells. We therefore hypothesized that bleomycin might perturb Golgi-operated GAG biosynthesis. Methods: We used stable isotope labeling coupled with LC/MS analysis of GAG disaccharides simultaneously from bleomycin-treated and non-treated cancer cells. To further understand the cytotoxicity of bleomycin and its relationship to GAGs, we used sodium chlorate to inhibit GAG sulfation and commercially available GAGs to compete for cell surface GAG/bleomycin interactions in seven cell lines including CHO745 defective in both heparan sulfate and chondroitin sulfate biosynthesis. Results: we discovered that heparan sulfate GAG was significantly undersulfated and the quantity and disaccharide compositions of GAGs were changed in bleomycin-treated cells in a concentration- and time-dependent manner. We revealed that bleomycin-induced cytotoxicity was directly related to cell surface GAGs. Conclusion: GAGs were targeted by bleomycin both at cell surface and at Golgi. Thus, GAGs might be the biological relevant molecules that might be related to the bleomycin-induced fibrosis in certain cancer patients, a severe side effect with largely unknown molecular mechanism.
Bleomycin
Bleomycin
Bleomycin
Radioimmunoassay of bleomycin
A radioimmunoassay for bleomycin has been produced using 125l-labeled bleomycin and antisera raised in rabbits against a carbodiimide-catalyzed bleomycin-bovine serum albumin conjugate. 125l-Labeled bleomycin was synthesized by direct iodination of the drug using the chloramine-T technique. The standard curve of the assay was linear on a logit-log plot and the lower limit of sensitivity was 250 pg bleomycin sulfate. A mean recovery of 102.6% (+/- 3.3% S.E.) was obtained using bleomycin added to normal sera. No significant decrease in bleomycin immunoreactivity was observed following 24 hr incubation of the drug in serum at 37 degrees. The radioimmunoassay was also suitable for measuring bleomycin in the presence of other drugs since the assay was not significantly affected by the other antineoplastic agents tested. The sensitivity and specificity of the radioimmunoassay for bleomycin should provide a new means for pharmacokinetic and toxicity studies of bleomycin.