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.
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]
| 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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| 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。
Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
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