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Identification
NameBleomycin
Accession NumberDB00290  (APRD00453, EXPT00718)
TypeSmall Molecule
GroupsApproved
Description

A 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.

Structure
Thumb
Synonyms
Bleocin
Bleomicin
Bleomicina
Bleomycin A2
Bleomycine
Bleomycinum
BLM
External Identifiers Not Available
Approved Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Blenoxane Pws 15unitpowder for solution15 unitintramuscular; intravenousBristol Labs Division Of Bristol Myers Squibb1973-12-312011-10-19Canada
Bleomycin for Injectionpowder for solution15 unitintra-arterial; intramuscular; intrapleural; intravenous; subcutaneousFresenius Kabi Canada Ltd2009-03-20Not applicableCanada
Bleomycin for Injection USPpowder for solution15 unitintramuscular; intrapleural; intravenous; subcutaneousSandoz Canada IncorporatedNot applicableNot applicableCanada
Bleomycin Sulphate for Injection USPpowder for solution15 unitintra-arterial; intracavitary; intramuscular; intravenous; subcutaneousHospira Healthcare Corporation1998-03-12Not applicableCanada
Approved Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Bleomycininjection, powder, lyophilized, for solution30 [USP'U]/1intramuscular; intrapleural; intravenous; subcutaneousHospira Worldwide, Inc.2000-03-10Not applicableUs
Bleomycininjection, powder, lyophilized, for solution30 [USP'U]/1intramuscular; intrapleural; intravenous; subcutaneousTeva Parenteral Medicines, Inc.2000-06-30Not applicableUs
Bleomycininjection, powder, lyophilized, for solution15 [USP'U]/1intramuscular; intrapleural; intravenous; subcutaneousTeva Parenteral Medicines, Inc.2000-06-30Not applicableUs
Bleomycininjection, powder, lyophilized, for solution30 [USP'U]/1intramuscular; intrapleural; intravenous; subcutaneousFresenius Kabi USA, LLC2009-02-13Not applicableUs
Bleomycininjection, powder, lyophilized, for solution15 [USP'U]/1intramuscular; intrapleural; intravenous; subcutaneousFresenius Kabi USA, LLC2009-02-13Not applicableUs
Bleomycininjection, powder, lyophilized, for solution15 [USP'U]/1intramuscular; intrapleural; intravenous; subcutaneousHospira Worldwide, Inc.2000-03-10Not applicableUs
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International Brands
NameCompany
BlenoxaneNot Available
BleoNot Available
Brand mixturesNot Available
Salts
Name/CASStructureProperties
Bleomycin sulfate
9041-93-4
Thumb
  • InChI Key:
  • Monoisotopic Mass:
  • Average Mass:
DBSALT000196
Categories
UNII40S1VHN69B
CAS number11056-06-7
WeightAverage: 1415.552
Monoisotopic: 1414.518979905
Chemical FormulaC55H84N17O21S3
InChI KeyInChIKey=OYVAGSVQBOHSSS-WXFSZRTFSA-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
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
SMILES
C[C@@H](O)[[email protected]](NC(=O)[C@@H](C)[[email protected]](O)[C@@H](C)NC(=O)[C@@H](NC(=O)C1=C(C)C(N)=NC(=N1)[[email protected]](CC(N)=O)NC[[email protected]](N)C(N)=O)[C@@H](OC1OC(CO)C(O)C(O)C1OC1OC(CO)C(O)C(OC(N)=O)C1O)C1=CN=CN1)C(=O)NCCC1=NC(=CS1)C1=NC(=CS1)C(=O)NCCC[S+](C)C
Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as hybrid glycopeptides. These are compounds containing a carbohydrate component linked linked to a hybrid peptide component.
KingdomOrganic compounds
Super ClassOrganic acids and derivatives
ClassCarboxylic acids and derivatives
Sub ClassAmino acids, peptides, and analogues
Direct ParentHybrid glycopeptides
Alternative Parents
Substituents
  • Hybrid glycopeptide
  • 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
  • O-glycosyl compound
  • Glycosyl compound
  • Disaccharide
  • Beta amino acid or derivatives
  • Alpha-amino acid or derivatives
  • N-substituted-alpha-amino acid
  • Pyrimidine-6-carboxylic acid or derivatives
  • Thiazolecarboxylic acid or derivatives
  • Thiazolecarboxamide
  • Aralkylamine
  • Aminopyrimidine
  • 2,4-disubstituted 1,3-thiazole
  • Fatty acyl
  • Imidolactam
  • Pyrimidine
  • Primary aromatic amine
  • Oxane
  • N-acyl-amine
  • Fatty amide
  • Saccharide
  • Heteroaromatic compound
  • Thiazole
  • Imidazole
  • Azole
  • Secondary carboxylic acid amide
  • Secondary alcohol
  • Primary carboxylic acid amide
  • Carboxamide group
  • 1,2-diol
  • Oxacycle
  • Azacycle
  • Organoheterocyclic compound
  • Secondary amine
  • Secondary aliphatic amine
  • Carboxylic acid amide
  • Acetal
  • Hydrocarbon derivative
  • Primary amine
  • Primary alcohol
  • Organosulfur compound
  • Organooxygen compound
  • Organonitrogen compound
  • Primary aliphatic amine
  • Carbonyl group
  • Amine
  • Alcohol
  • Organic cation
  • Aromatic heteromonocyclic compound
Molecular FrameworkAromatic heteromonocyclic compounds
External Descriptors
Pharmacology
IndicationFor palliative treatment in the management malignant neoplasm (trachea, bronchus, lung), squamous cell carcinoma, and lymphomas.
PharmacodynamicsBleomycin is an antibiotic which has been shown to have antitumor activity. Bleomycin selectively inhibits the synthesis of deoxyribonucleic acid (DNA). The guanine and cytosine content correlates with the degree of mitomycin-induced cross-linking. At high concentrations of the drug, cellular RNA and protein synthesis are also suppressed. Bleomycin has been shown in vitro to inhibit B cell, T cell, and macrophage proliferation and impair antigen presentation, as well as the secretion of interferon gamma, TNFa, and IL-2. The antibiotic antitumor drugs are cell cycle-nonspecific except for Bleomycin (which has major effects in G2 and M phases).
Mechanism of actionAlthough the exact mechanism of action of bleomycin is unknown, available evidence would seem to indicate that the main mode of action is the inhibition of DNA synthesis with some evidence of lesser inhibition of RNA and protein synthesis. DNA cleavage by bleomycin depends on oxygen and metal ions, at least in vitro. It is believed that bleomycin chelates metal ions (primarily iron) producing a pseudoenzyme that reacts with oxygen to produce superoxide and hydroxide free radicals that cleave DNA.
Related Articles
AbsorptionSystemic absorption is approximately 45%.
Volume of distributionNot Available
Protein binding1%
Metabolism

Hepatic

Route of eliminationIt was reported that patients with moderately severe renal failure excreted less than 20% of the dose in the urine.
Half life115 minutes
ClearanceNot Available
ToxicityExcessive 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.
Affected organisms
  • Humans and other mammals
PathwaysNot Available
SNP Mediated Effects
Interacting Gene/EnzymeSNP RS IDAllele nameDefining changeEffectReference(s)
Bleomycin hydrolase
Gene symbol: BLMH
UniProt: Q13867
rs10500565 Not AvailableA AlleleImproved response to bleomycin18398146
Bleomycin hydrolase
Gene symbol: BLMH
UniProt: Q13867
rs10500565 Not AvailableG AlleleReduced response to bleomycin, higher prevalence of relapse18398146
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption-0.8877
Blood Brain Barrier-0.9732
Caco-2 permeable-0.6551
P-glycoprotein substrateSubstrate0.853
P-glycoprotein inhibitor INon-inhibitor0.8781
P-glycoprotein inhibitor IINon-inhibitor0.8454
Renal organic cation transporterNon-inhibitor0.9331
CYP450 2C9 substrateNon-substrate0.7773
CYP450 2D6 substrateNon-substrate0.7966
CYP450 3A4 substrateSubstrate0.6154
CYP450 1A2 substrateNon-inhibitor0.7423
CYP450 2C9 inhibitorNon-inhibitor0.7035
CYP450 2D6 inhibitorNon-inhibitor0.8678
CYP450 2C19 inhibitorNon-inhibitor0.6794
CYP450 3A4 inhibitorNon-inhibitor0.67
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.8609
Ames testAMES toxic0.772
CarcinogenicityNon-carcinogens0.8957
BiodegradationNot ready biodegradable0.8863
Rat acute toxicity2.6132 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.991
hERG inhibition (predictor II)Inhibitor0.6172
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397 )
Pharmacoeconomics
Manufacturers
  • Bristol myers squibb co pharmaceutical research institute
  • App pharmaceuticals llc
  • Bedford laboratories div ben venue laboratories inc
  • Hospira inc
  • Pharmachemie bv
  • Teva parenteral medicines inc
Packagers
Dosage forms
FormRouteStrength
Powder for solutionintramuscular; intravenous15 unit
Injection, powder, lyophilized, for solutionintramuscular; intrapleural; intravenous; subcutaneous15 [USP'U]/1
Injection, powder, lyophilized, for solutionintramuscular; intrapleural; intravenous; subcutaneous30 [USP'U]/1
Powder for solutionintra-arterial; intramuscular; intrapleural; intravenous; subcutaneous15 unit
Powder for solutionintramuscular; intrapleural; intravenous; subcutaneous15 unit
Powder for solutionintra-arterial; intracavitary; intramuscular; intravenous; subcutaneous15 unit
Prices
Unit descriptionCostUnit
Blenoxane 30 unit vial584.83USD vial
Blenoxane 15 unit vial292.42USD vial
Bleomycin sulfate 30 unit vial120.0USD vial
Bleomycin sulfate 15 unit vial81.6USD vial
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
PatentsNot Available
Properties
StateSolid
Experimental Properties
PropertyValueSource
melting point71 °CNot Available
water solubilitySolubleNot Available
Predicted Properties
PropertyValueSource
Water Solubility0.0282 mg/mLALOGPS
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 Å2ChemAxon
Rotatable Bond Count36ChemAxon
Refractivity344.16 m3·mol-1ChemAxon
Polarizability142.03 Å3ChemAxon
Number of Rings6ChemAxon
Bioavailability0ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Not Available
SpectraNot Available
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.

USRE0304514
General References
  1. Claussen CA, Long EC: Nucleic Acid recognition by metal complexes of bleomycin. Chem Rev. 1999 Sep 8;99(9):2797-816. [PubMed:11749501 ]
External Links
ATC CodesL01DC01
AHFS Codes
  • 10:00.00
PDB Entries
FDA labelDownload (46.3 KB)
MSDSDownload (34.4 KB)
Interactions
Drug Interactions
Drug
Brentuximab vedotinThe risk or severity of adverse effects can be increased when Brentuximab vedotin is combined with Bleomycin.
DenosumabThe risk or severity of adverse effects can be increased when Denosumab is combined with Bleomycin.
FilgrastimThe risk or severity of adverse effects can be increased when Filgrastim is combined with Bleomycin.
Filgrastim-sndzThe risk or severity of adverse effects can be increased when Filgrastim-sndz is combined with Bleomycin.
GemcitabineThe risk or severity of adverse effects can be increased when Gemcitabine is combined with Bleomycin.
LeflunomideThe risk or severity of adverse effects can be increased when Bleomycin is combined with Leflunomide.
NatalizumabThe risk or severity of adverse effects can be increased when Bleomycin is combined with Natalizumab.
PhenytoinThe serum concentration of Phenytoin can be decreased when it is combined with Bleomycin.
PimecrolimusThe risk or severity of adverse effects can be increased when Pimecrolimus is combined with Bleomycin.
RoflumilastRoflumilast may increase the immunosuppressive activities of Bleomycin.
SargramostimThe risk or severity of adverse effects can be increased when Sargramostim is combined with Bleomycin.
Sipuleucel-TThe therapeutic efficacy of Sipuleucel-T can be decreased when used in combination with Bleomycin.
TacrolimusThe risk or severity of adverse effects can be increased when Tacrolimus is combined with Bleomycin.
TofacitinibBleomycin may increase the immunosuppressive activities of Tofacitinib.
TrastuzumabTrastuzumab may increase the neutropenic activities of Bleomycin.
Food InteractionsNot Available

Targets

Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
inhibitor
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. [PubMed:17202402 ]
2. DNA
Kind
Nucleotide
Organism
Human
Pharmacological action
yes
Actions
cleavage
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. [PubMed: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. [PubMed: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. [PubMed: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. [PubMed:6177398 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
inhibitor
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. [PubMed:17202402 ]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
substrate
General Function:
Cysteine-type peptidase activity
Specific Function:
The normal physiological role of BLM hydrolase is unknown, but it catalyzes the inactivation of the antitumor drug BLM (a glycopeptide) by hydrolyzing the carboxamide bond of its B-aminoalaninamide moiety thus protecting normal and malignant cells from BLM toxicity.
Gene Name:
BLMH
Uniprot ID:
Q13867
Molecular Weight:
52561.93 Da
References
  1. Lazo JS, Boland CJ, Schwartz PE: Bleomycin hydrolase activity and cytotoxicity in human tumors. Cancer Res. 1982 Oct;42(10):4026-31. [PubMed:6179595 ]
  2. Lefterov IM, Koldamova RP, King J, Lazo JS: The C-terminus of human bleomycin hydrolase is required for protection against bleomycin-induced chromosomal damage. Mutat Res. 1998 Oct 12;421(1):1-7. [PubMed:9748474 ]
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Drug created on June 13, 2005 07:24 / Updated on August 17, 2016 12:23