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Record Information
Version2.0
Creation Date2009-07-21 20:26:29 UTC
Update Date2014-12-24 20:25:51 UTC
Accession NumberT3D2738
Identification
Common NameBleomycin
ClassSmall Molecule
DescriptionA complex of related glycopeptide antibiotics from Streptomyces verticillus consisting of bleomycin A2 and B2 (B2 CAS # 9060-10-0). It inhibits DNA metabolism and is used as an antineoplastic, especially for solid tumors. Bleomycin A2 is used as the representative structure for Bleomycin.
Compound Type
  • Amide
  • Amine
  • Antibiotic, Antineoplastic
  • Antimetabolite
  • Drug
  • Ester
  • Lachrymator
  • Metabolite
  • Organic Compound
  • Synthetic Compound
Chemical Structure
Thumb
Synonyms
Synonym
Blenoxane
Bleo
Bleocin
Bleomicin
Bleomicina
Bleomycin A2
Bleomycin sulfate
Bleomycin sulphate
Bleomycine
Bleomycinum
BLM
Chemical FormulaC55H84N17O21S3
Average Molecular Mass1415.551 g/mol
Monoisotopic Mass1414.518 g/mol
CAS Registry Number11056-06-7
IUPAC Name(3-{[2-(2-{2-[(2S,3R)-2-[(2S,3S,4R)-4-[(2S,3R)-2-({6-amino-2-[(1S)-1-{[(2S)-2-amino-2-carbamoylethyl]amino}-2-carbamoylethyl]-5-methylpyrimidin-4-yl}formamido)-3-[(3-{[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)propanamido]-3-hydroxy-2-methylpentanamido]-3-hydroxybutanamido]ethyl}-1,3-thiazol-4-yl)-1,3-thiazol-4-yl]formamido}propyl)dimethylsulfanium
Traditional Namebleomycin
SMILES[H][C@](C)(O)[C@]([H])(N=C(O)[C@@]([H])(C)[C@]([H])(O)[C@@]([H])(C)N=C(O)[C@@]([H])(N=C(O)C1=C(C)C(=N)NC(=N1)[C@]([H])(CC(O)=N)NC[C@]([H])(N)C(O)=N)[C@@]([H])(OC1([H])OC([H])(CO)C([H])(O)C([H])(O)C1([H])OC1([H])OC([H])(CO)C([H])(O)C([H])(OC(O)=N)C1([H])O)C1=CN=CN1)C(O)=NCCC1=NC(=CS1)C1=NC(=CS1)C(O)=NCCC[S+](C)C
InChI IdentifierInChI=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 KeyInChIKey=OYVAGSVQBOHSSS-WXFSZRTFSA-O
Chemical Taxonomy
Description belongs to the class of organic compounds known as hybrid glycopeptides. Hybrid glycopeptides are compounds containing a carbohydrate component linked to a hybrid peptide component.
KingdomOrganic compounds
Super ClassOrganic acids and derivatives
ClassPeptidomimetics
Sub ClassHybrid peptides
Direct ParentHybrid glycopeptides
Alternative Parents
Substituents
  • Hybrid glycopeptide
  • Histidine or derivatives
  • Fatty acyl glycoside of mono- or disaccharide
  • Fatty acyl glycoside
  • N-acyl-alpha amino acid or derivatives
  • Gamma amino acid or derivatives
  • Alpha-amino acid amide
  • Beta amino acid or derivatives
  • O-glycosyl compound
  • Glycosyl compound
  • Disaccharide
  • N-substituted-alpha-amino acid
  • Alpha-amino acid or derivatives
  • Pyrimidine-6-carboxylic acid or derivatives
  • 2-heteroaryl carboxamide
  • Thiazolecarboxamide
  • Thiazolecarboxylic acid or derivatives
  • Aralkylamine
  • 2,4-disubstituted 1,3-thiazole
  • Aminopyrimidine
  • Fatty amide
  • Fatty acyl
  • N-acyl-amine
  • Imidolactam
  • Oxane
  • Pyrimidine
  • Azole
  • Carbamic acid ester
  • Heteroaromatic compound
  • Thiazole
  • Imidazole
  • Secondary alcohol
  • Carboxamide group
  • Carbonic acid derivative
  • Amino acid or derivatives
  • Secondary carboxylic acid amide
  • Primary carboxylic acid amide
  • Organoheterocyclic compound
  • Secondary aliphatic amine
  • Oxacycle
  • Acetal
  • Carboxylic acid derivative
  • Azacycle
  • Secondary amine
  • Organic nitrogen compound
  • Organic oxygen compound
  • Primary aliphatic amine
  • Organonitrogen compound
  • Organooxygen compound
  • Carbonyl group
  • Organosulfur compound
  • Primary alcohol
  • Primary amine
  • Amine
  • Hydrocarbon derivative
  • Organic oxide
  • Organopnictogen compound
  • Alcohol
  • Organic cation
  • Aromatic heteromonocyclic compound
Molecular FrameworkAromatic heteromonocyclic compounds
External Descriptors
Biological Properties
StatusDetected and Not Quantified
OriginExogenous
Cellular Locations
  • Cytoplasm
  • Membrane
Biofluid LocationsNot Available
Tissue LocationsNot Available
PathwaysNot Available
Applications
Biological Roles
Chemical RolesNot Available
Physical Properties
StateSolid
AppearanceWhite powder.
Experimental Properties
PropertyValue
Melting Point71°C
Boiling PointNot Available
SolubilitySoluble
LogPNot Available
Predicted Properties
PropertyValueSource
Water Solubility0.028 g/LALOGPS
logP-0.52ALOGPS
logP-9.7ChemAxon
logS-4.7ALOGPS
pKa (Strongest Acidic)11.34ChemAxon
pKa (Strongest Basic)7.67ChemAxon
Physiological Charge2ChemAxon
Hydrogen Acceptor Count28ChemAxon
Hydrogen Donor Count20ChemAxon
Polar Surface Area627.07 ŲChemAxon
Rotatable Bond Count36ChemAxon
Refractivity344.16 m³·mol⁻¹ChemAxon
Polarizability142.03 ųChemAxon
Number of Rings6ChemAxon
Bioavailability0ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash KeyView
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-0002-5519000000-a9e7e590fae8c464ce36JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-05fr-5918000000-5ca154887c83cf983142JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-05fr-5925010000-dfb06a8f5285854a7878JSpectraViewer
Toxicity Profile
Route of ExposureIntravenous; systemic absorption is approximately 45%.
Mechanism of ToxicityIt has been suggested that bleomycin induces sensitivity to oxygen toxicity and recent studies support the role of the proinflammatory cytokines IL-18 and IL-1beta in the mechanism of bleomycin-induced lung injury. (Wikipedia) In primary pulmonary endothelial cells, bleomycin initiates apoptosis via the extrinsic pathway (2). In relation to bleomycin-induced scleroderma, bleomycin exerts various effects on skin-constituted cells such as fibroblasts, keratinocytes, and endothelial cells, as well as immunocytes. Bleomycin upregulates gene expression of ECM proteins as well as fibrogenic cytokines such as TGF-β and CTGF in cultured human skin fibroblasts. Also, in vitro studies showed a dose-dependent stimulation of endothelial cell secretion of collagen synthesis by bleomycin, which was inhibited by the anti-TGF-β antibody. (3).
MetabolismHepatic Route of Elimination: It was reported that patients with moderately severe renal failure excreted less than 20% of the dose in the urine. Half Life: 115 minutes
Toxicity ValuesNot Available
Lethal DoseNot Available
Carcinogenicity (IARC Classification)2B, possibly carcinogenic to humans. (6)
Uses/SourcesFor palliative treatment in the management malignant neoplasm (trachea, bronchus, lung), squamous cell carcinoma, and lymphomas.
Minimum Risk LevelNot Available
Health EffectsThe most serious complication of bleomycin is pulmonary fibrosis and impaired lung function. (Wikipedia) Bleomycin can also induce scleroderma (4, 2).
SymptomsExcessive exposure may cause fever, chills, nausea, vomiting, mental, confusion, and wheezing. Bleomycin may cause irritation to eyes, skin and respiratory tract. It may also cause a darkening or thickening of the skin. It may cause an allergic reaction.
TreatmentNot Available
Normal Concentrations
Not Available
Abnormal Concentrations
Not Available
DrugBank IDDB00290
HMDB IDHMDB14435
PubChem Compound ID5360373
ChEMBL IDCHEMBL403664
ChemSpider ID4514492
KEGG IDC06854
UniProt IDNot Available
OMIM ID
ChEBI ID22907
BioCyc IDNot Available
CTD IDNot Available
Stitch IDBleomycin
PDB IDBLM
ACToR IDNot Available
Wikipedia LinkBleomycin
References
Synthesis Reference

Hamao Umezawa, Kenji Maeda, Tomohisa Takita, Yuya Nakayama, Akio Fujii, Nobuyoshi Shimada, Hideo Chimura, “Novel process for producing antibiotics bleomycin.” U.S. Patent USRE0304514, issued October, 1970.

MSDSLink
General References
  1. Claussen CA, Long EC: Nucleic Acid recognition by metal complexes of bleomycin. Chem Rev. 1999 Sep 8;99(9):2797-816. [11749501 ]
  2. Mungunsukh O, Griffin AJ, Lee YH, Day RM: Bleomycin induces the extrinsic apoptotic pathway in pulmonary endothelial cells. Am J Physiol Lung Cell Mol Physiol. 2010 May;298(5):L696-703. doi: 10.1152/ajplung.00322.2009. Epub 2010 Feb 12. [20154224 ]
  3. Yamamoto T, Katayama I: Vascular changes in bleomycin-induced scleroderma. Int J Rheumatol. 2011;2011:270938. doi: 10.1155/2011/270938. Epub 2011 Oct 19. [22028717 ]
  4. Finch WR, Rodnan GP, Buckingham RB, Prince RK, Winkelstein A: Bleomycin-induced scleroderma. J Rheumatol. 1980 Sep-Oct;7(5):651-9. [6160247 ]
  5. Drugs.com [Link]
  6. International Agency for Research on Cancer (2014). IARC Monographs on the Evaluation of Carcinogenic Risks to Humans. [Link]
Gene Regulation
Up-Regulated Genes
GeneGene SymbolGene IDInteractionChromosomeDetails
Down-Regulated Genes
GeneGene SymbolGene IDInteractionChromosomeDetails

Targets

1. DNA
General Function:
Used for biological information storage.
Specific Function:
DNA contains the instructions needed for an organism to develop, survive and reproduce.
Molecular Weight:
2.15 x 1012 Da
References
  1. Ma Q, Akiyama Y, Xu Z, Konishi K, Hecht SM: Identification and cleavage site analysis of DNA sequences bound strongly by bleomycin. J Am Chem Soc. 2009 Feb 11;131(5):2013-22. doi: 10.1021/ja808629s. [19146404 ]
  2. Chow MS, Liu LV, Solomon EI: Further insights into the mechanism of the reaction of activated bleomycin with DNA. Proc Natl Acad Sci U S A. 2008 Sep 9;105(36):13241-5. doi: 10.1073/pnas.0806378105. Epub 2008 Aug 29. [18757754 ]
  3. Akiyama Y, Ma Q, Edgar E, Laikhter A, Hecht SM: Identification of strong DNA binding motifs for bleomycin. J Am Chem Soc. 2008 Jul 30;130(30):9650-1. doi: 10.1021/ja802905g. Epub 2008 Jul 3. [18597467 ]
  4. Mirabelli CK, Ting A, Huang CH, Mong S, Crooke ST: Bleomycin and talisomycin sequence-specific strand scission of DNA: a mechanism of double-strand cleavage. Cancer Res. 1982 Jul;42(7):2779-85. [6177398 ]
General Function:
Metal ion binding
Specific Function:
DNA ligase that seals nicks in double-stranded DNA during DNA replication, DNA recombination and DNA repair.
Gene Name:
LIG1
Uniprot ID:
P18858
Molecular Weight:
101735.11 Da
References
  1. Rose JL, Reeves KC, Likhotvorik RI, Hoyt DG: Base excision repair proteins are required for integrin-mediated suppression of bleomycin-induced DNA breakage in murine lung endothelial cells. J Pharmacol Exp Ther. 2007 Apr;321(1):318-26. Epub 2007 Jan 3. [17202402 ]
General Function:
Zinc ion binding
Specific Function:
Isoform 3 functions as heterodimer with DNA-repair protein XRCC1 in the nucleus and can correct defective DNA strand-break repair and sister chromatid exchange following treatment with ionizing radiation and alkylating agents. Isoform 1 is targeted to mitochondria, where it functions as DNA ligase in mitochondrial base-excision DNA repair (PubMed:10207110, PubMed:24674627).
Gene Name:
LIG3
Uniprot ID:
P49916
Molecular Weight:
112905.96 Da
References
  1. Rose JL, Reeves KC, Likhotvorik RI, Hoyt DG: Base excision repair proteins are required for integrin-mediated suppression of bleomycin-induced DNA breakage in murine lung endothelial cells. J Pharmacol Exp Ther. 2007 Apr;321(1):318-26. Epub 2007 Jan 3. [17202402 ]
General Function:
Temperature-gated cation channel activity
Specific Function:
Receptor-activated non-selective cation channel involved in detection of pain and possibly also in cold perception and inner ear function (PubMed:25389312, PubMed:25855297). Has a central role in the pain response to endogenous inflammatory mediators and to a diverse array of volatile irritants, such as mustard oil, cinnamaldehyde, garlic and acrolein, an irritant from tears gas and vehicule exhaust fumes (PubMed:25389312, PubMed:20547126). Is also activated by menthol (in vitro)(PubMed:25389312). Acts also as a ionotropic cannabinoid receptor by being activated by delta(9)-tetrahydrocannabinol (THC), the psychoactive component of marijuana (PubMed:25389312). May be a component for the mechanosensitive transduction channel of hair cells in inner ear, thereby participating in the perception of sounds. Probably operated by a phosphatidylinositol second messenger system (By similarity).
Gene Name:
TRPA1
Uniprot ID:
O75762
Molecular Weight:
127499.88 Da
References
  1. Nilius B, Prenen J, Owsianik G: Irritating channels: the case of TRPA1. J Physiol. 2011 Apr 1;589(Pt 7):1543-9. doi: 10.1113/jphysiol.2010.200717. Epub 2010 Nov 15. [21078588 ]