Identification

Name
Bleomycin
Accession Number
DB00290  (APRD00453, EXPT00718)
Type
Small Molecule
Groups
Approved
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
Product Ingredients
IngredientUNIICASInChI Key
Bleomycin sulfate7DP3NTV15T9041-93-4WUIABRMSWOKTOF-OCBSMOPSSA-N
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 unitIntramuscular; Intrapleural; Intravenous; SubcutaneousFresenius Kabi2009-03-20Not applicableCanada
Bleomycin for Injection USPPowder, for solution15 unitIntra-arterial; Intracavitary; Intramuscular; Intravenous; SubcutaneousPfizer1998-03-12Not applicableCanada
Bleomycin for Injection USPPowder, for solution15 unitIntramuscular; Intrapleural; Intravenous; SubcutaneousSandoz Canada IncorporatedNot applicableNot applicableCanada
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
BleomycinInjection, powder, lyophilized, for solution30 [USP'U]/1Intramuscular; Intrapleural; Intravenous; SubcutaneousHospira, Inc.2000-03-10Not applicableUs
BleomycinInjection, powder, lyophilized, for solution30 [USP'U]/1Intramuscular; Intrapleural; Intravenous; SubcutaneousFresenius Kabi2009-02-13Not applicableUs
BleomycinInjection, powder, lyophilized, for solution15 [USP'U]/1Intramuscular; Intrapleural; Intravenous; SubcutaneousHospira, Inc.2000-03-10Not applicableUs
BleomycinInjection, powder, lyophilized, for solution15 [USP'U]/1Intramuscular; Intrapleural; Intravenous; SubcutaneousTeva Parenteral Medicines, Inc.2000-06-30Not applicableUs
BleomycinInjection, powder, lyophilized, for solution15 [USP'U]/1Intramuscular; Intrapleural; Intravenous; SubcutaneousFresenius Kabi2009-02-13Not applicableUs
BleomycinInjection, powder, lyophilized, for solution30 [USP'U]/1Intramuscular; Intrapleural; Intravenous; SubcutaneousTeva Parenteral Medicines, Inc.2000-06-30Not applicableUs
International/Other Brands
Blenoxane / Bleo
Categories
UNII
40S1VHN69B
CAS number
11056-06-7
Weight
Average: 1415.552
Monoisotopic: 1414.518979905
Chemical Formula
C55H84N17O21S3
InChI Key
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[[email protected]@H](O)[[email protected]](NC(=O)[[email protected]@H](C)[[email protected]](O)[[email protected]@H](C)NC(=O)[[email protected]@H](NC(=O)C1=C(C)C(N)=NC(=N1)[[email protected]](CC(N)=O)NC[[email protected]](N)C(N)=O)[[email protected]@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

Pharmacology

Indication

For palliative treatment in the management malignant neoplasm (trachea, bronchus, lung), squamous cell carcinoma, and lymphomas.

Structured Indications
Pharmacodynamics

Bleomycin 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 action

Although 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.

TargetActionsOrganism
UDNA ligase 1
inhibitor
Human
ADNA
cleavage
Human
UDNA ligase 3
inhibitor
Human
Absorption

Systemic absorption is approximately 45%.

Volume of distribution
Not Available
Protein binding

1%

Metabolism

Hepatic

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

Clearance
Not Available
Toxicity

Excessive 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
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Interacting Gene/EnzymeAllele nameGenotype(s)Defining Change(s)Type(s)DescriptionDetails
Bleomycin hydrolase---(G;G)G AlleleEffect Directly StudiedPatients with this genotype have reduced survival time and increased frequency of early relapse when using bleomycin to treat testicular cancer.Details

Interactions

Drug Interactions
DrugInteractionDrug group
AcetyldigitoxinAcetyldigitoxin may decrease the cardiotoxic activities of Bleomycin.Approved
AcetyldigoxinAcetyldigoxin may decrease the cardiotoxic activities of Bleomycin.Experimental
BCG vaccineThe therapeutic efficacy of BCG vaccine can be decreased when used in combination with Bleomycin.Investigational
BevacizumabBevacizumab may increase the cardiotoxic activities of Bleomycin.Approved, Investigational
Brentuximab vedotinThe risk or severity of adverse effects can be increased when Brentuximab vedotin is combined with Bleomycin.Approved
CabazitaxelThe risk or severity of adverse effects can be increased when Cabazitaxel is combined with Bleomycin.Approved
Clostridium tetani toxoid antigen (formaldehyde inactivated)The therapeutic efficacy of Clostridium tetani toxoid antigen (formaldehyde inactivated) can be decreased when used in combination with Bleomycin.Approved
Corynebacterium diphtheriae toxoid antigen (formaldehyde inactivated)The therapeutic efficacy of Corynebacterium diphtheriae toxoid antigen (formaldehyde inactivated) can be decreased when used in combination with Bleomycin.Approved
CyclophosphamideCyclophosphamide may increase the cardiotoxic activities of Bleomycin.Approved, Investigational
CymarinCymarin may decrease the cardiotoxic activities of Bleomycin.Experimental
DenosumabThe risk or severity of adverse effects can be increased when Denosumab is combined with Bleomycin.Approved
DeslanosideDeslanoside may decrease the cardiotoxic activities of Bleomycin.Approved
DigitoxinDigitoxin may decrease the cardiotoxic activities of Bleomycin.Approved, Investigational
DigoxinDigoxin may decrease the cardiotoxic activities of Bleomycin.Approved
Digoxin Immune Fab (Ovine)Digoxin Immune Fab (Ovine) may decrease the cardiotoxic activities of Bleomycin.Approved
DocetaxelThe risk or severity of adverse effects can be increased when Docetaxel is combined with Bleomycin.Approved, Investigational
FilgrastimThe risk or severity of adverse effects can be increased when Filgrastim is combined with Bleomycin.Approved
FingolimodBleomycin may increase the immunosuppressive activities of Fingolimod.Approved, Investigational
G17DTThe therapeutic efficacy of G17DT can be decreased when used in combination with Bleomycin.Investigational
GemcitabineThe risk or severity of adverse effects can be increased when Gemcitabine is combined with Bleomycin.Approved
GI-5005The therapeutic efficacy of GI-5005 can be decreased when used in combination with Bleomycin.Investigational
GitoformateGitoformate may decrease the cardiotoxic activities of Bleomycin.Experimental
Hepatitis A VaccineThe therapeutic efficacy of Hepatitis A Vaccine can be decreased when used in combination with Bleomycin.Approved
Hepatitis B Vaccine (Recombinant)The therapeutic efficacy of Hepatitis B Vaccine (Recombinant) can be decreased when used in combination with Bleomycin.Approved, Withdrawn
INGN 201The therapeutic efficacy of INGN 201 can be decreased when used in combination with Bleomycin.Investigational
INGN 225The therapeutic efficacy of INGN 225 can be decreased when used in combination with Bleomycin.Investigational
Lanatoside CLanatoside C may decrease the cardiotoxic activities of Bleomycin.Experimental
LeflunomideThe risk or severity of adverse effects can be increased when Bleomycin is combined with Leflunomide.Approved, Investigational
MetildigoxinMetildigoxin may decrease the cardiotoxic activities of Bleomycin.Experimental
NatalizumabThe risk or severity of adverse effects can be increased when Bleomycin is combined with Natalizumab.Approved, Investigational
OleandrinOleandrin may decrease the cardiotoxic activities of Bleomycin.Experimental, Investigational
OuabainOuabain may decrease the cardiotoxic activities of Bleomycin.Approved
PaclitaxelThe risk or severity of adverse effects can be increased when Paclitaxel is combined with Bleomycin.Approved, Vet Approved
PeruvosidePeruvoside may decrease the cardiotoxic activities of Bleomycin.Experimental
PhenytoinThe serum concentration of Phenytoin can be decreased when it is combined with Bleomycin.Approved, Vet Approved
PimecrolimusThe risk or severity of adverse effects can be increased when Pimecrolimus is combined with Bleomycin.Approved, Investigational
ProscillaridinProscillaridin may decrease the cardiotoxic activities of Bleomycin.Experimental
Rabies virus inactivated antigen, AThe risk or severity of adverse effects can be increased when Bleomycin is combined with Rabies virus inactivated antigen, A.Approved
Rabies virus inactivated antigen, AThe therapeutic efficacy of Rabies virus inactivated antigen, A can be decreased when used in combination with Bleomycin.Approved
RindopepimutThe therapeutic efficacy of Rindopepimut can be decreased when used in combination with Bleomycin.Investigational
RoflumilastRoflumilast may increase the immunosuppressive activities of Bleomycin.Approved
Rotavirus VaccineThe therapeutic efficacy of Rotavirus Vaccine can be decreased when used in combination with Bleomycin.Approved
Rubella virus vaccineThe therapeutic efficacy of Rubella virus vaccine can be decreased when used in combination with Bleomycin.Approved
Salmonella typhi ty21a live antigenThe therapeutic efficacy of Salmonella typhi ty21a live antigen can be decreased when used in combination with Bleomycin.Approved
SargramostimThe risk or severity of adverse effects can be increased when Sargramostim is combined with Bleomycin.Approved, Investigational
Sipuleucel-TThe therapeutic efficacy of Sipuleucel-T can be decreased when used in combination with Bleomycin.Approved
SRP 299The therapeutic efficacy of SRP 299 can be decreased when used in combination with Bleomycin.Investigational
TacrolimusThe risk or severity of adverse effects can be increased when Tacrolimus is combined with Bleomycin.Approved, Investigational
TecemotideThe therapeutic efficacy of Tecemotide can be decreased when used in combination with Bleomycin.Investigational
TG4010The therapeutic efficacy of TG4010 can be decreased when used in combination with Bleomycin.Investigational
TofacitinibBleomycin may increase the immunosuppressive activities of Tofacitinib.Approved, Investigational
TrastuzumabTrastuzumab may increase the cardiotoxic activities of Bleomycin.Approved, Investigational
Yellow fever vaccineThe therapeutic efficacy of Yellow fever vaccine can be decreased when used in combination with Bleomycin.Approved
Zoster vaccineThe therapeutic efficacy of Zoster vaccine can be decreased when used in combination with Bleomycin.Approved
Food Interactions
Not 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
Human Metabolome Database
HMDB14435
KEGG Compound
C06854
PubChem Compound
5360373
PubChem Substance
46509116
ChemSpider
4514492
BindingDB
50122169
ChEBI
22907
ChEMBL
CHEMBL403664
Therapeutic Targets Database
DAP000531
PharmGKB
PA448645
HET
BLM
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Bleomycin
ATC Codes
L01DC01 — Bleomycin
AHFS Codes
  • 10:00.00 — Antineoplastic Agents
FDA label
Download (46.3 KB)
MSDS
Download (34.4 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1CompletedTreatmentCutaneous or Sub-cutaneous Malignancies1
1CompletedTreatmentHodgkins Disease (HD)1
1CompletedTreatmentHuman Immunodeficiency Virus (HIV) Infections / Kaposi s Sarcoma (KS)3
1CompletedTreatmentHuman Immunodeficiency Virus (HIV) Infections / Non-Hodgkin's Lymphoma (NHL)1
1CompletedTreatmentNeoplasms, Head and Neck / Skin Neoplasms1
1RecruitingTreatmentLymphoma, Hodgkins1
1TerminatedTreatmentCNS Metastases / Metastatic Brain Tumors1
1Unknown StatusTreatmentMalignant Lymphomas1
1Unknown StatusTreatmentMelanoma (Skin)1
1WithdrawnTreatmentMalignant Neoplasm of Pancreas1
1, 2Unknown StatusTreatmentMalignant Lymphomas1
2Active Not RecruitingTreatmentGerm Cell Tumors1
2Active Not RecruitingTreatmentHodgkins Disease (HD)1
2Active Not RecruitingTreatmentLymphoma, Hodgkins3
2Active Not RecruitingTreatmentMalignant Lymphomas1
2Active Not RecruitingTreatmentMalignant Lymphomas / Nonneoplastic Condition1
2CompletedTreatmentCancer, Ovarian / Childhood Germ Cell Tumor / Drug/Agent Toxicity by Tissue/Organ / Extragonadal Germ Cell Tumor1
2CompletedTreatmentExtragonadal Germ Cell Tumor / Teratoma / Testicular germ cell tumour2
2CompletedTreatmentGerm Cell Tumors / Testicular Neoplasms1
2CompletedTreatmentHodgkins Disease (HD) / Human Immunodeficiency Virus (HIV) Infections1
2CompletedTreatmentHodgkins Disease (HD) / Lymphoma, Hodgkin Disease / Lymphoma, Hodgkins / Malignant Lymphomas1
2CompletedTreatmentHodgkins Disease (HD) / Pediatric1
2CompletedTreatmentHuman Immunodeficiency Virus (HIV) Infections / Kaposi s Sarcoma (KS)1
2CompletedTreatmentLymphoma, Hodgkins1
2CompletedTreatmentMalignant Lymphomas9
2CompletedTreatmentMalignant Lymphomas / Multiple Myeloma and Plasma Cell Neoplasm1
2RecruitingTreatmentHead Neck Cancer1
2RecruitingTreatmentIntracranial Germinoma1
2RecruitingTreatmentIntracranial Non-germinomatous Germ Cell Tumor1
2RecruitingTreatmentLymphoma, Hodgkins1
2RecruitingTreatmentOvarian Granulosa Cell Tumor / Ovarian Gynandroblastoma / Ovarian Sertoli-Leydig Cell Tumors / Ovarian Sex Cord Tumor With Annular Tubules / Ovarian Sex Cord-Stromal Tumor / Ovarian Sex Cord-Stromal Tumor of Mixed or Unclassified Cell Types / Ovarian Steroid Cell Tumor1
2TerminatedTreatmentBrain and Central Nervous System Tumors1
2TerminatedTreatmentCarcinoma, Squamous Cell of Head and Neck / Recurrent Head and Neck Cancer1
2TerminatedTreatmentHodgkins Disease (HD)1
2TerminatedTreatmentMalignant Lymphomas1
2Unknown StatusTreatmentHIV-associated Hodgkin Lymphoma1
2Unknown StatusTreatmentHodgkins Disease (HD)1
2Unknown StatusTreatmentMalignant Lymphomas3
2WithdrawnTreatmentMalignant Lymphomas1
2WithdrawnTreatmentUlcerated Cutaneous Metastases1
2, 3Unknown StatusTreatmentExtragonadal Germ Cell Tumor / Teratoma / Testicular germ cell tumour1
3Active Not RecruitingTreatmentChildhood Embryonal Tumor / Childhood Extracranial Germ Cell Tumor / Childhood Extragonadal Germ Cell Tumor / Childhood Malignant Ovarian Germ Cell Tumor / Childhood Malignant Testicular Germ Cell Tumor / Childhood Teratoma / Ovarian Embryonal Carcinoma / Ovarian Yolk Sac Tumor / Stage II Malignant Testicular Germ Cell Tumor / Stage IIA Ovarian Germ Cell Tumor / Stage IIB Ovarian Germ Cell Tumor / Stage IIC Ovarian Germ Cell Tumor / Stage III Malignant Testicular Germ Cell Tumor / Stage IIIA Ovarian Germ Cell Tumor / Stage IIIB Ovarian Germ Cell Tumor / Stage IIIC Ovarian Germ Cell Tumor / Testicular Choriocarcinoma and Yolk Sac Tumor / Testicular Embryonal Carcinoma1
3Active Not RecruitingTreatmentChildhood Nodular Lymphocyte Predominant Hodgkin Lymphoma / Stage III Childhood Hodgkin Lymphoma / Stage IV Childhood Hodgkin Lymphoma1
3Active Not RecruitingTreatmentDiffuse Large B Cell Lymphoma CD20 Positive / Diffuse Large B Cell Lymphoma CD20+1
3Active Not RecruitingTreatmentLymphoma, Hodgkins4
3Active Not RecruitingTreatmentMalignant Lymphomas6
3CompletedSupportive CareMetastatic Cancers1
3CompletedTreatmentCardiac Toxicity / Malignant Lymphomas2
3CompletedTreatmentCervical Cancers1
3CompletedTreatmentChildhood Germ Cell Tumor / Extragonadal Germ Cell Tumor / Testicular germ cell tumour1
3CompletedTreatmentChildhood Lymphocyte-Depleted Classical Hodgkin Lymphoma / Childhood Mixed Cellularity Classical Hodgkin Lymphoma / Childhood Nodular Lymphocyte Predominant Hodgkin Lymphoma / Childhood Nodular Sclerosis Classical Hodgkin Lymphoma / Malignant Lymphomas / Stage I Childhood Hodgkin Lymphoma / Stage II Childhood Hodgkin Lymphoma / Stage III Childhood Hodgkin Lymphoma / Stage IV Childhood Hodgkin Lymphoma1
3CompletedTreatmentDrug/Agent Toxicity by Tissue/Organ / Testicular germ cell tumour1
3CompletedTreatmentHead and Neck Carcinoma1
3CompletedTreatmentHodgkins Disease (HD)1
3CompletedTreatmentHuman Immunodeficiency Virus (HIV) Infections / Kaposi s Sarcoma (KS)2
3CompletedTreatmentHuman Immunodeficiency Virus (HIV) Infections / Non-Hodgkin's Lymphoma (NHL)1
3CompletedTreatmentLymphoma, Hodgkins5
3CompletedTreatmentMalignant Lymphomas4
3CompletedTreatmentMediastinal Cancer / Metastatic Cancers / Testicular germ cell tumour1
3Enrolling by InvitationTreatmentCancer, Ovarian / Neoplasms, Ovarian / Ovarian Germ Cell Cancer1
3Enrolling by InvitationTreatmentCancer, Ovarian / Neoplasms, Ovarian / Ovarian Sex Cord Stromal Tumor1
3RecruitingTreatmentAdult Germ Cell Tumor / Childhood Extracranial Germ Cell Tumor / Childhood Germ Cell Tumor / Extragonadal Embryonal Carcinoma / Grade 2 Immature Ovarian Teratoma / Grade 3 Immature Ovarian Teratoma / Malignant Germ Cell Tumor / Stage I Ovarian Choriocarcinoma / Stage I Ovarian Embryonal Carcinoma / Stage I Ovarian Teratoma / Stage I Ovarian Yolk Sac Tumor / Stage I Testicular Choriocarcinoma / Stage I Testicular Embryonal Carcinoma / Stage I Testicular Yolk Sac Tumor / Stage II Ovarian Choriocarcinoma / Stage II Ovarian Embryonal Carcinoma / Stage II Ovarian Yolk Sac Tumor / Stage II Testicular Choriocarcinoma / Stage II Testicular Embryonal Carcinoma / Stage II Testicular Yolk Sac Tumor / Stage III Ovarian Choriocarcinoma / Stage III Ovarian Embryonal Carcinoma / Stage III Ovarian Yolk Sac Tumor / Stage III Testicular Choriocarcinoma / Stage III Testicular Embryonal Carcinoma / Stage III Testicular Yolk Sac Tumor / Stage IV Ovarian Choriocarcinoma / Stage IV Ovarian Embryonal Carcinoma / Stage IV Ovarian Yolk Sac Tumor / Testicular Mixed Choriocarcinoma and Embryonal Carcinoma / Testicular Mixed Choriocarcinoma and Teratoma / Testicular Mixed Choriocarcinoma and Yolk Sac Tumor1
3RecruitingTreatmentChildhood Hodgkin Lymphoma / Classical Hodgkin Lymphoma / Stage IIB Hodgkin Lymphoma / Stage IIIB Hodgkin Lymphoma / Stage IV Hodgkin Lymphoma / Stage IVA Hodgkin Lymphoma / Stage IVB Hodgkin Lymphoma1
3RecruitingTreatmentClassical Hodgkin Lymphoma1
3RecruitingTreatmentGerm Cell Tumors1
3RecruitingTreatmentInfection, Human Immunodeficiency Virus I1
3RecruitingTreatmentLymphoma, Hodgkins1
3RecruitingTreatmentLymphoma, Large B-Cell, Diffuse (DLBCL)1
3TerminatedTreatmentMalignant Lymphomas2
3Unknown StatusTreatmentCancer, Ovarian / Childhood Germ Cell Tumor / Extragonadal Germ Cell Tumor1
3Unknown StatusTreatmentExtragonadal Germ Cell Tumor / Teratoma / Testicular germ cell tumour1
3Unknown StatusTreatmentHuman Immunodeficiency Virus (HIV) Infections / Kaposi s Sarcoma (KS)1
3Unknown StatusTreatmentLymphoma, Hodgkins1
3Unknown StatusTreatmentMalignant Lymphomas4
4CompletedTreatmentCancers1
4CompletedTreatmentHead and Neck Carcinoma1
4RecruitingTreatmentVenous Malformations1
Not AvailableCompletedTreatmentChildhood Germ Cell Tumor / Extragonadal Germ Cell Tumor1
Not AvailableCompletedTreatmentHuman Immunodeficiency Virus (HIV) Infections / Non-Hodgkin's Lymphoma (NHL)1
Not AvailableNot Yet RecruitingNot AvailableCancer, Treatment-Related / Cardiovascular Morbidity / Toxicity Due to Chemotherapy1
Not AvailableUnknown StatusTreatmentBrain and Central Nervous System Tumors / Cancer, Ovarian / Childhood Germ Cell Tumor / Extragonadal Germ Cell Tumor1
Not AvailableUnknown StatusTreatmentMalignant Lymphomas2

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; Intracavitary; Intramuscular; Intravenous; Subcutaneous15 unit
Powder, for solutionIntramuscular; Intrapleural; 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.
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)71 °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 FiveNoChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleYesChemAxon
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)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available

Taxonomy

Description
This compound belongs to the class of organic compounds known as hybrid glycopeptides. These are compounds containing a carbohydrate component linked to a hybrid peptide component.
Kingdom
Organic compounds
Super Class
Organic acids and derivatives
Class
Peptidomimetics
Sub Class
Hybrid peptides
Direct Parent
Hybrid glycopeptides
Alternative Parents
Histidine and derivatives / Fatty acyl glycosides of mono- and disaccharides / N-acyl-alpha amino acids and derivatives / Gamma amino acids and derivatives / Alpha amino acid amides / Beta amino acids and derivatives / Disaccharides / O-glycosyl compounds / Pyrimidinecarboxylic acids and derivatives / 2-heteroaryl carboxamides
show 26 more
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
show 50 more
Molecular Framework
Aromatic heteromonocyclic compounds
External Descriptors
Non-ribosomal peptide/polyketide hybrids (LMPK14000006)

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
Uniprot Name
DNA ligase 1
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 rad...
Gene Name
LIG3
Uniprot ID
P49916
Uniprot Name
DNA ligase 3
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...
Gene Name
BLMH
Uniprot ID
Q13867
Uniprot Name
Bleomycin hydrolase
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]

Drug created on June 13, 2005 07:24 / Updated on November 19, 2017 20:33