BLEOMYCIN

First approved in 1973

Description
Sources: http://news.cancerconnect.com/wp-content/uploads/2010/06/bleomycin.pdf | https://www.accessdata.fda.gov/drugsatfda_docs/label/2010/050443s036lbl.pdfhttp://www.drugbank.ca/drugs/DB00290#targets
Curator's Comment: description was created based on several sources, including, http://www.accessdata.fda.gov/drugsatfda_docs/label/2010/050443s036lbl.pdf

Bleomycin is a mixture of cytotoxic glycopeptide antibiotics isolated from a strain of Streptomyces verticillus. Bleomycin has 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).

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
DNA 241 Target ID: CHEMBL2311221 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2010/050443s036lbl.pdf	Inhibitor 8146		20.0 µM [Kd]
DNA 241 Target ID: CHEMBL2311221 Sources: https://www.ncbi.nlm.nih.gov/pubmed/18597467 \| https://www.accessdata.fda.gov/drugsatfda_docs/label/2010/050443s036lbl.pdf \| https://www.ncbi.nlm.nih.gov/pubmed/50602	Inhibitor 8146

Conditions

Condition	Modality	Highest Phase	Product
Squamous cell carcinoma 7 Sources: http://news.cancerconnect.com/wp-content/uploads/2010/06/bleomycin.pdf	Primary	Approved 8307	BLEOMYCIN SULFATE Approved Use Bleomycin for Injection, USP should be considered a palliative treatment. It has been shown to be useful in the management of the following neoplasms either as a single agent or in proven combinations with other approved chemotherapeutic agents: Squamous Cell Carcinoma: Head and neck (including mouth, tongue, tonsil, nasopharynx, oropharynx, sinus, palate, lip, buccal mucosa, gingivae, epiglottis, skin, larynx), penis, cervix, and vulva. The response to Bleomycin for Injection is poorer in patients with previously irradiated head and neck cancer. Lymphomas: Hodgkin’s disease, non-Hodgkin’s lymphoma. Testicular Carcinoma: Embryonal cell, choriocarcinoma, and teratocarcinoma. Bleomycin for Injection, USP has also been shown to be useful in the management of: Malignant Pleural Effusion: Bleomycin for Injection is effective as a sclerosing agent for the treatment of malignant pleural effusion and prevention of recurrent pleural effusions. Launch Date 1.12924803E11
Hodgkin's lymphoma 34 Sources: http://news.cancerconnect.com/wp-content/uploads/2010/06/bleomycin.pdf	Primary	Approved 8307	BLEOMYCIN SULFATE Approved Use Bleomycin for Injection, USP should be considered a palliative treatment. It has been shown to be useful in the management of the following neoplasms either as a single agent or in proven combinations with other approved chemotherapeutic agents: Squamous Cell Carcinoma: Head and neck (including mouth, tongue, tonsil, nasopharynx, oropharynx, sinus, palate, lip, buccal mucosa, gingivae, epiglottis, skin, larynx), penis, cervix, and vulva. The response to Bleomycin for Injection is poorer in patients with previously irradiated head and neck cancer. Lymphomas: Hodgkin’s disease, non-Hodgkin’s lymphoma. Testicular Carcinoma: Embryonal cell, choriocarcinoma, and teratocarcinoma. Bleomycin for Injection, USP has also been shown to be useful in the management of: Malignant Pleural Effusion: Bleomycin for Injection is effective as a sclerosing agent for the treatment of malignant pleural effusion and prevention of recurrent pleural effusions. Launch Date 1.12924803E11
Non-Hodgkin's lymphoma 79 Sources: http://news.cancerconnect.com/wp-content/uploads/2010/06/bleomycin.pdf	Primary	Approved 8307	BLEOMYCIN SULFATE Approved Use Bleomycin for Injection, USP should be considered a palliative treatment. It has been shown to be useful in the management of the following neoplasms either as a single agent or in proven combinations with other approved chemotherapeutic agents: Squamous Cell Carcinoma: Head and neck (including mouth, tongue, tonsil, nasopharynx, oropharynx, sinus, palate, lip, buccal mucosa, gingivae, epiglottis, skin, larynx), penis, cervix, and vulva. The response to Bleomycin for Injection is poorer in patients with previously irradiated head and neck cancer. Lymphomas: Hodgkin’s disease, non-Hodgkin’s lymphoma. Testicular Carcinoma: Embryonal cell, choriocarcinoma, and teratocarcinoma. Bleomycin for Injection, USP has also been shown to be useful in the management of: Malignant Pleural Effusion: Bleomycin for Injection is effective as a sclerosing agent for the treatment of malignant pleural effusion and prevention of recurrent pleural effusions. Launch Date 1.12924803E11
Testicular cancer 7 Sources: https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=b5806c40-12ce-48e3-8abd-9f8997ef4428&type=display	Primary	Approved 8307	BLEOMYCIN SULFATE Approved Use Bleomycin for Injection, USP should be considered a palliative treatment. It has been shown to be useful in the management of the following neoplasms either as a single agent or in proven combinations with other approved chemotherapeutic agents: Squamous Cell Carcinoma: Head and neck (including mouth, tongue, tonsil, nasopharynx, oropharynx, sinus, palate, lip, buccal mucosa, gingivae, epiglottis, skin, larynx), penis, cervix, and vulva. The response to Bleomycin for Injection is poorer in patients with previously irradiated head and neck cancer. Lymphomas: Hodgkin’s disease, non-Hodgkin’s lymphoma. Testicular Carcinoma: Embryonal cell, choriocarcinoma, and teratocarcinoma. Bleomycin for Injection, USP has also been shown to be useful in the management of: Malignant Pleural Effusion: Bleomycin for Injection is effective as a sclerosing agent for the treatment of malignant pleural effusion and prevention of recurrent pleural effusions. Launch Date 1.12924803E11
Malignant pleural effusion 6 Sources: https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=b5806c40-12ce-48e3-8abd-9f8997ef4428&type=display	Primary	Approved 8307	BLEOMYCIN SULFATE Approved Use Bleomycin for Injection, USP should be considered a palliative treatment. It has been shown to be useful in the management of the following neoplasms either as a single agent or in proven combinations with other approved chemotherapeutic agents: Squamous Cell Carcinoma: Head and neck (including mouth, tongue, tonsil, nasopharynx, oropharynx, sinus, palate, lip, buccal mucosa, gingivae, epiglottis, skin, larynx), penis, cervix, and vulva. The response to Bleomycin for Injection is poorer in patients with previously irradiated head and neck cancer. Lymphomas: Hodgkin’s disease, non-Hodgkin’s lymphoma. Testicular Carcinoma: Embryonal cell, choriocarcinoma, and teratocarcinoma. Bleomycin for Injection, USP has also been shown to be useful in the management of: Malignant Pleural Effusion: Bleomycin for Injection is effective as a sclerosing agent for the treatment of malignant pleural effusion and prevention of recurrent pleural effusions. Launch Date 1.12924803E11
Head and neck squamous cell carcinoma 31 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2010/050443s036lbl.pdf	Primary	Approved 8307	BLENOXANE Approved Use BLENOXANE should be considered a palliative treatment. It has been shown to be useful in the management of the following neoplasms either as a single agent or in proven combinations with other approved chemotherapeutic agent:Squamous Cell Carcinoma, Lymphomas, Testicular Carcinoma, Malignant Pleural Effusion. Launch Date 1.74355202E11
Malignant pleural effusion 6 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2010/050443s036lbl.pdf	Primary	Approved 8307	BLENOXANE Approved Use BLENOXANE should be considered a palliative treatment. It has been shown to be useful in the management of the following neoplasms either as a single agent or in proven combinations with other approved chemotherapeutic agent:Squamous Cell Carcinoma, Lymphomas, Testicular Carcinoma, Malignant Pleural Effusion. Launch Date 1.74355202E11
Embryonal cell, choriocarcinoma 5 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2010/050443s036lbl.pdf	Primary	Approved 8307	BLENOXANE Approved Use BLENOXANE should be considered a palliative treatment. It has been shown to be useful in the management of the following neoplasms either as a single agent or in proven combinations with other approved chemotherapeutic agent:Squamous Cell Carcinoma, Lymphomas, Testicular Carcinoma, Malignant Pleural Effusion. Launch Date 1.74355202E11
Teratocarcinoma 5 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2010/050443s036lbl.pdf	Primary	Approved 8307	BLENOXANE Approved Use BLENOXANE should be considered a palliative treatment. It has been shown to be useful in the management of the following neoplasms either as a single agent or in proven combinations with other approved chemotherapeutic agent:Squamous Cell Carcinoma, Lymphomas, Testicular Carcinoma, Malignant Pleural Effusion. Launch Date 1.74355202E11
Hodgkin's lymphoma 34 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2010/050443s036lbl.pdf	Primary	Approved 8307	BLENOXANE Approved Use BLENOXANE should be considered a palliative treatment. It has been shown to be useful in the management of the following neoplasms either as a single agent or in proven combinations with other approved chemotherapeutic agent:Squamous Cell Carcinoma, Lymphomas, Testicular Carcinoma, Malignant Pleural Effusion. Launch Date 1.74355202E11
Non-Hodgkin's lymphoma 79 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2010/050443s036lbl.pdf	Primary	Approved 8307	BLENOXANE Approved Use BLENOXANE should be considered a palliative treatment. It has been shown to be useful in the management of the following neoplasms either as a single agent or in proven combinations with other approved chemotherapeutic agent:Squamous Cell Carcinoma, Lymphomas, Testicular Carcinoma, Malignant Pleural Effusion. Launch Date 1.74355202E11
Squamous cell carcinoma, penis 5 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2010/050443s036lbl.pdf	Primary	Approved 8307	BLENOXANE Approved Use BLENOXANE should be considered a palliative treatment. It has been shown to be useful in the management of the following neoplasms either as a single agent or in proven combinations with other approved chemotherapeutic agent:Squamous Cell Carcinoma, Lymphomas, Testicular Carcinoma, Malignant Pleural Effusion. Launch Date 1.74355202E11
Squamous cell carcinoma, cervix 5 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2010/050443s036lbl.pdf	Primary	Approved 8307	BLENOXANE Approved Use BLENOXANE should be considered a palliative treatment. It has been shown to be useful in the management of the following neoplasms either as a single agent or in proven combinations with other approved chemotherapeutic agent:Squamous Cell Carcinoma, Lymphomas, Testicular Carcinoma, Malignant Pleural Effusion. Launch Date 1.74355202E11
Squamous cell carcinoma, vulva 5 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2010/050443s036lbl.pdf	Primary	Approved 8307	BLENOXANE Approved Use BLENOXANE should be considered a palliative treatment. It has been shown to be useful in the management of the following neoplasms either as a single agent or in proven combinations with other approved chemotherapeutic agent:Squamous Cell Carcinoma, Lymphomas, Testicular Carcinoma, Malignant Pleural Effusion. Launch Date 1.74355202E11

PubMed

Title	Date	PubMed
Biochemical effects of bleomycin A2 on Novikoff hepatoma ascites cells.	1975	50602
Ultrastructural study of the effect of bleomycin A2 on the nucleolus and its possibly related cytoplasmic constituents in Novikoff hepatoma cells.	1975 Feb	45894
Hypomagnesemia, renal dysfunction, and Raynaud's phenomenon in patients treated with cisplatin, vinblastine, and bleomycin.	1985 Dec 15	2413982
[Raynaud's disease after treatment with bleomycin and vinblastine].	1986 Feb 17	2423995
Renovascular hypertension after combination chemotherapy for testicular cancer.	1988 Jan	2447295
Acute vascular toxicity after combination chemotherapy with cisplatin, vinblastine, and bleomycin for testicular cancer.	1988 May	2456930
Drug-induced encephalopathy after previous ifosfamide treatment.	1988 Nov 5	2460709
Pulmonary emboli in patients receiving chemotherapy for non-Hodgkin's lymphoma.	1988 Sep	2457470
Hemolytic uremic syndrome following cisplatin, bleomycin, and vincristine chemotherapy: a report of a case and a review of the literature.	1989	2482985
Raynaud's phenomenon in patients treated with cisplatin, vinblastine, and bleomycin for germ cell cancer: measurement of vasoconstrictor response to cold.	1989 Jul	2472472
Long-term neurotoxicity in patients treated with cisplatin, vinblastine, and bleomycin for metastatic germ cell cancer.	1989 Oct	2476531
Two cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine plus extended-field radiotherapy is superior to radiotherapy alone in early favorable Hodgkin's lymphoma: final results of the GHSG HD7 trial.	2007 Aug 10	17606976
Telomerase activity is required for bleomycin-induced pulmonary fibrosis in mice.	2007 Dec	18008008
Early lung injury contributes to lung fibrosis via AT1 receptor in rats.	2007 Feb	17241526
Dexrazoxane-associated risk for acute myeloid leukemia/myelodysplastic syndrome and other secondary malignancies in pediatric Hodgkin's disease.	2007 Feb 10	17290056
Are platinum-based chemotherapeutic drugs safe for patients with Charcot-Marie-Tooth disease?	2007 Jun	17565539
Characterization of DNA reactive and non-DNA reactive anticancer drugs by gene expression profiling.	2007 Jun 1	17374387
Effects of curcumin in treatment of experimental pulmonary fibrosis: a comparison with hydrocortisone.	2007 Jun 13	17434272
An essential role for CCAAT/enhancer binding protein beta in bleomycin-induced pulmonary fibrosis.	2007 Mar	17177178
FDG-PET in bleomycin-induced pneumonitis following ABVD chemotherapy for Hodgkin's disease--a useful tool for monitoring pulmonary toxicity and disease activity.	2007 Nov	18024389
Hodgkin lymphoma presenting with various immunologic abnormalities, including autoimmune hepatitis, Hashimoto's thyroiditis, autoimmune hemolytic anemia, and immune thrombocytopenia.	2008 Feb	18501091
DNA methylation inhibitor 5-Aza-2'-deoxycytidine induces reversible genome-wide DNA damage that is distinctly influenced by DNA methyltransferases 1 and 3B.	2008 Jan	17991895
Cerebellar dysfunction caused by procarbazine and consumption of excessive amount of bananas.	2008 Jun	18293384
PPAR-gamma agonists inhibit profibrotic phenotypes in human lung fibroblasts and bleomycin-induced pulmonary fibrosis.	2008 May	18162602
Agents associated with lung inflammation induce similar responses in NCI-H292 lung epithelial cells.	2008 Oct	18684396
Simvastatin attenuates bleomycin-induced pulmonary fibrosis in mice.	2008 Sep 20	19080365
Radiation-induced cathepsin S is involved in radioresistance.	2009 Apr 15	19101991
Bleomycin-induced nuclear factor-kappaB activation in human bronchial epithelial cells involves the phosphorylation of glycogen synthase kinase 3beta.	2009 Jun 22	19429264
Effects of erlotinib on lung injury induced by intratracheal administration of bleomycin (BLM) in rats.	2010 Aug	20686337
XRCC1 deficiency sensitizes human lung epithelial cells to genotoxicity by crocidolite asbestos and Libby amphibole.	2010 Dec	20705543
Influence of p53 expression on sensitivity of cancer cells to bleomycin.	2010 Jul-Aug	20135637
The D prostanoid receptor agonist BW245C [(4S)-(3-[(3R,S)-3-cyclohexyl-3-hydroxypropyl]-2,5-dioxo)-4-imidazolidineheptanoic acid] inhibits fibroblast proliferation and bleomycin-induced lung fibrosis in mice.	2010 Nov	20719937
C/EBPβ-Thr217 phosphorylation signaling contributes to the development of lung injury and fibrosis in mice.	2011	21998664
Essential role of MeCP2 in the regulation of myofibroblast differentiation during pulmonary fibrosis.	2011 Apr	21435439
Anti-inflammatory and antifibrotic effects of methyl palmitate.	2011 Aug 1	21575650
Pulmonary fibrosis inducer, bleomycin, causes redox-sensitive activation of phospholipase D and cytotoxicity through formation of bioactive lipid signal mediator, phosphatidic acid, in lung microvascular endothelial cells.	2011 Feb	21131602
Links between DNA polymerase beta expression and sensitivity to bleomycin.	2011 Mar 15	21251944
Removal of reactive oxygen species-induced 3'-blocked ends by XPF-ERCC1.	2011 Nov 21	22007867
Testing chemical agents with the cytokinesis-block micronucleus cytome assay.	2012	23249641
Thymoquinone blocks lung injury and fibrosis by attenuating bleomycin-induced oxidative stress and activation of nuclear factor Kappa-B in rats.	2012 Dec 16	22982510
The ToxTracker assay: novel GFP reporter systems that provide mechanistic insight into the genotoxic properties of chemicals.	2012 Jan	22003191
Assessment of Brd4 inhibition in idiopathic pulmonary fibrosis lung fibroblasts and in vivo models of lung fibrosis.	2013 Aug	23759512
Comparison of bleomycin-induced pulmonary apoptosis between NMRI mice and C57BL/6 mice.	2013 Jan	24459475
Suppression of nuclear factor erythroid 2-related factor 2 via extracellular signal-regulated kinase contributes to bleomycin-induced oxidative stress and fibrogenesis.	2013 Jun 20	23570914
Matrix metalloproteinase Mmp-1a is dispensable for normal growth and fertility in mice and promotes lung cancer progression by modulating inflammatory responses.	2013 May 17	23548910
Berberine attenuates bleomycin induced pulmonary toxicity and fibrosis via suppressing NF-κB dependant TGF-β activation: a biphasic experimental study.	2013 May 23	23523906
Diallylsulfide attenuates excessive collagen production and apoptosis in a rat model of bleomycin induced pulmonary fibrosis through the involvement of protease activated receptor-2.	2013 Sep 1	23656969
Direct activation of ATM by resveratrol under oxidizing conditions.	2014	24933654
Distinct mechanisms of cell-kill by triapine and its terminally dimethylated derivative Dp44mT due to a loss or gain of activity of their copper(II) complexes.	2014 Oct 1	25130544
Protocatechuic aldehyde ameliorates experimental pulmonary fibrosis by modulating HMGB1/RAGE pathway.	2015 Feb 15	25582705

Patents

Sample Use Guides

In Vivo Use Guide

The main components of Bleomycin for Injection are bleomycins A2 and B2. Squamous cell carcinoma, non-Hodgkin’s lymphoma, testicular carcinoma - 0.25 to 0.50 units/kg (10 to 20 units/m2) given intravenously, intramuscularly, or subcutaneously weekly or twice weekly.

Route of Administration: Other

In Vitro Use Guide

Purified nucleolar DNA was markedly degraded at a concentration of 13 ug/ml by bleomycin A2; bleomycin concentrations 20-30 times greater were required to degrade nucleoplasmic DNA. Whole nuclear DNA was degraded to only a small extent at 13 ug/ml but was markedly degraded at higher bleomycin concentrations.

Name

Type

Language

BLEOMYCIN

Official Name

English

Bleomycin [WHO-DD]

Common Name

English

BLEOMYCIN HYDROCHLORIDE [JAN]

Common Name

English

BLEOMYCIN [VANDF]

Common Name

English

BLENAMAX

Brand Name

English

NSC-125066

Code

English

BLEOMYCINS

Common Name

English

bleomycin [INN]

Common Name

English

BLEOMYCINS [MI]

Common Name

English

BLEOMYCIN [IARC]

Common Name

English

BLEOMYCIN [HSDB]

Common Name

English

BLEOMYCIN HEXAL

Brand Name

English

BLEO

Brand Name

English

BLEOCIN

Brand Name

English

BLEOMYCINS [IARC]

Common Name

English

MIXTURE OF CYTOTOXIC GLYCOPEPTIDES PRODUCED BY THE GROWTH OF STREPTOMYCES VERTICILLUS

Common Name

English

Classification Tree Code System Code

LIVERTOX

NBK548499