Bleomycin A2
* Please be kindly noted products are not for therapeutic use. We do not sell to patients.
| Category | Antibiotics |
| Catalog number | BBF-04363 |
| CAS | 11116-31-7 |
| Molecular Weight | 1415.55 |
| Molecular Formula | C55H84N17O21S3 |
| Purity | ≥95.0% |
Online Inquiry
Description
It is one of two components found in the glycopeptide antineoplastic antibiotic Bleomycin sulfate. Bleomycin sulfate is a chemotherapeutic agent used for the treatment of hodgkins lymphoma. It is isolated from the bacterium Streptomyces verticillus.
Specification
| Synonyms | Bleomycin a2; Bleomycinamide, N1-[3-(dimethylsulfonio)propyl]-; Bleogin; N1-[3-(Dimethylsulfonio)propyl]bleomycinamide; Pingyangmycin A2; Zhengguangmycin A2 |
| Storage | Store at -20°C |
| IUPAC Name | 3-[[2-[2-[2-[[(2S,3R)-2-[[(2S,3S,4R)-4-[[(2S,3R)-2-[[6-amino-2-[(1S)-3-amino-1-[[(2S)-2,3-diamino-3-oxopropyl]amino]-3-oxopropyl]-5-methylpyrimidine-4-carbonyl]amino]-3-[(2R,3S,4S,5S,6S)-3-[(2R,3S,4S,5R,6R)-4-carbamoyloxy-3,5-dihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy-4,5-dihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy-3-(1H-imidazol-5-yl)propanoyl]amino]-3-hydroxy-2-methylpentanoyl]amino]-3-hydroxybutanoyl]amino]ethyl]-1,3-thiazol-4-yl]-1,3-thiazole-4-carbonyl]amino]propyl-dimethylsulfanium |
| 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)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 |
| InChI | InChI=1S/C55H83N17O21S3/c1-20-33(69-46(72-44(20)58)25(12-31(57)76)64-13-24(56)45(59)82)50(86)71-35(41(26-14-61-19-65-26)91-54-43(39(80)37(78)29(15-73)90-54)92-53-40(81)42(93-55(60)88)38(79)30(16-74)89-53)51(87)66-22(3)36(77)21(2)47(83)70-34(23(4)75)49(85)63-10-8-32-67-28(18-94-32)52-68-27(17-95-52)48(84)62-9-7-11-96(5)6/h14,17-19,21-25,29-30,34-43,53-54,64,73-75,77-81H,7-13,15-16,56H2,1-6H3,(H13-,57,58,59,60,61,62,63,65,66,69,70,71,72,76,82,83,84,85,86,87,88)/p+1/t21-,22+,23+,24-,25-,29-,30+,34-,35-,36-,37+,38+,39-,40-,41-,42-,43-,53+,54-/m0/s1 |
| InChI Key | OYVAGSVQBOHSSS-UAPAGMARSA-O |
| Source | Streptomyces verticillus |
Properties
| Appearance | White to Off-white Crystalline Powder |
| Antibiotic Activity Spectrum | Neoplastics (Tumor) |
| Solubility | Soluble in Water (20 mg/mL) |
Reference Reading
1. Role of carbohydrate moiety of bleomycin-A2 in caspase-3 activation and internucleosomal chromatin fragmentation in apoptosis of laryngeal carcinoma cells
Abderraouf Kenani, Souhir Brahim, Kaouthar Abid Cell Biol Int . 2008 Feb;32(2):171-7. doi: 10.1016/j.cellbi.2007.08.032.
Bleomycin (BLM), an antitumor antibiotic, is currently used during anticancer therapy. The therapeutic efficiency of BLM for the treatment of malignant tumors is related to its ability to cleave DNA. However, little is known about the biological activity of the glycannic moiety in BLM-induced cytotoxicity. In this study, cell death induced by BLM-A2 and deglycosylated BLM-A2 was studied in a laryngeal carcinoma cell line (HEp-2 cells). Our results indicate that HEp-2 cells showed morphological and biochemical changes associated with apoptosis in the presence of low concentrations of BLM-A2. In contrast, the same changes, except activation of caspase-3 and internucleosomal digestion of genomic DNA, were observed when cells were exposed to high concentrations of deglycosylated BLM-A2. These observations indicate that the glycannic moiety from the bleomycin molecule has important biological effects on the cytotoxicity of the drug.
2. Intralesional Bleomycin Injections for Vascular Malformations: A Systematic Review and Meta-Analysis
Jim A Reekers, Irma M Rigter, Sophie E R Horbach, Phyllis I Spuls, Chantal M A M van der Horst, J Henk Sillevis Smitt Plast Reconstr Surg . 2016 Jan;137(1):244-256. doi: 10.1097/PRS.0000000000001924.
Background:Vascular malformations are congenital anomalies of the vascular system. Intralesional bleomycin injections are commonly used to treat vascular malformations. However, pulmonary fibrosis could potentially be a severe complication, known from systemic bleomycin therapy for malignancies. In this study, the authors investigate the effectiveness and safety of bleomycin (A2, B2, and A5) injections for vascular malformations, when possible relative to other sclerosants.Methods:The authors performed a PubMed, Embase, Cochrane Central Register of Controlled Trials, and gray literature search for studies (1995 to the present) reporting outcome of intralesional bleomycin injections in patients with vascular malformations (n ≥ 10). Predefined outcome measures of interest were size reduction, symptom relief, quality of life, adverse events (including pulmonary fibrosis), and patient satisfaction.Results:Twenty-seven studies enrolling 1325 patients were included. Quality of evidence was generally low. Good to excellent size reduction was reported in 84 percent of lymphatic and 87 percent of venous malformations. Pulmonary fibrosis was never encountered. Meta-analysis of four studies on venous malformations treated with bleomycin versus other sclerosants showed similar size reduction (OR, 0.67; 95 percent CI, 0.24 to 1.88) but a significantly lower adverse event rate (OR, 0.1; 95 percent CI, 0.03 to 0.39) and fewer severe complications after bleomycin. Symptom relief, quality of life, and patient satisfaction were reported inadequately.Conclusions:The authors' data suggest that bleomycin is effective in reducing the size of lymphatic and venous malformations, and leads to a lower adverse event rate and fewer severe complications than other sclerosants. The included literature does not provide evidence that pulmonary fibrosis is a complication of intralesional bleomycin injections. This study represents the "best available" evidence; however, only low- to moderate-quality studies were available.Clinical question/level of evidence:Therapeutic, IV.
3. Identification of ANXA2 (annexin A2) as a specific bleomycin target to induce pulmonary fibrosis by impeding TFEB-mediated autophagic flux
Kui Wang, Tao Zhang, Canhua Huang, Ke Xie, Wei Gao, Xiaofeng Zhu, Edouard C Nice, Haining Chen, Yong Peng, Min Wu, Na Xie, Yuan Liu, Xiang Liu, Jiang Lan, Yunlong Lei, Qiang Chen, Yuquan Wei, Jingwen Jiang, Xuefeng Li Autophagy . 2018;14(2):269-282. doi: 10.1080/15548627.2017.1409405.
Bleomycin is a clinically potent anticancer drug used for the treatment of germ-cell tumors, lymphomas and squamous-cell carcinomas. Unfortunately, the therapeutic efficacy of bleomycin is severely hampered by the development of pulmonary fibrosis. However, the mechanisms underlying bleomycin-induced pulmonary fibrosis, particularly the molecular target of bleomycin, remains unknown. Here, using a chemical proteomics approach, we identify ANXA2 (annexin A2) as a direct binding target of bleomycin. The interaction of bleomycin with ANXA2 was corroborated both in vitro and in vivo. Genetic depletion of anxa2 in mice mitigates bleomycin-induced pulmonary fibrosis. We further demonstrate that Glu139 (E139) of ANXA2 is required for bleomycin binding in lung epithelial cells. A CRISPR-Cas9-engineered ANXA2E139Amutation in lung epithelial cells ablates bleomycin binding and activates TFEB (transcription factor EB), a master regulator of macroautophagy/autophagy, resulting in substantial acceleration of autophagic flux. Pharmacological activation of TFEB elevates bleomycin-initiated autophagic flux, inhibits apoptosis and proliferation of epithelial cells, and ameliorates pulmonary fibrosis in bleomycin-treated mice. Notably, we observe lowered TFEB and LC3B levels in human pulmonary fibrosis tissues compared to normal controls, suggesting a critical role of TFEB-mediated autophagy in pulmonary fibrosis. Collectively, our data demonstrate that ANXA2 is a specific bleomycin target, and bleomycin binding with ANXA2 impedes TFEB-induced autophagic flux, leading to induction of pulmonary fibrosis. Our findings provide insight into the mechanisms of bleomycin-induced fibrosis and may facilitate development of optimized bleomycin therapeutics devoid of lung toxicity.
Recommended Products
| BBF-00764 | Cerebroside C | Inquiry |
| BBF-01825 | Loganin | Inquiry |
| BBF-03753 | Baicalin | Inquiry |
| BBF-03755 | Actinomycin D | Inquiry |
| BBF-00677 | 3-Amino-3-deoxy-D-glucose | Inquiry |
| BBF-02614 | Nystatin | Inquiry |
Bio Calculators
* Our calculator is based on the following equation:
Concentration (start) x Volume (start) = Concentration (final) x Volume (final)
It is commonly abbreviated as: C1V1 = C2V2
* Total Molecular Weight:
g/mol
Tip: Chemical formula is case sensitive. C22H30N4O √ c22h30n40 ╳
