DT-Web

DB00290 - Bleomycin


Identification
Name Bleomycin
Accession Number DB00290 (APRD00453, EXPT00718)
Type small molecule
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
MOL SDF PDB SMILES InChI
Categories (*)
Molecular Weight 1415.552
Groups approved
Monoisotopic Weight 1414.518979905
Pharmacology
Indication For palliative treatment in the management malignant neoplasm (trachea, bronchus, lung), squamous cell carcinoma, and lymphomas.
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.
Absorption Systemic absorption is approximately 45%.
Protein binding 1%
Biotransformation Hepatic
Route of elimination It was reported that patients with moderately severe renal failure excreted less than 20% of the dose in the urine.
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
Interactions
Drug Interactions
Drug Mechanism of interaction
BRENTUXIMAB VEDOTIN Pulmonary toxicity of bleomycin may be increased. Avoid combination.
Digoxin The antineoplasic agent decreases the effect of digoxin
Fosphenytoin The antineoplasic agent decreases the effect of hydantoin
Leflunomide Immunosuppressants like bleomycin may enhance the adverse/toxic effect of Leflunomide. Specifically, the risk for hematologic toxicity such as pancytopenia, agranulocytosis, and/or thrombocytopenia may be increased. Consider eliminating the use of a leflunomide loading dose in patients who are receiving other immunosuppressants in order to reduce the risk for serious adverse events such as hematologic toxicity.
Natalizumab Immunosuppressants like bleomycin may enhance the adverse/toxic effect of Natalizumab. Specifically, the risk of concurrent infection may be increased. Patients receiving natalizumab should not use concurrent immunosuppressants.
Phenytoin The antineoplasic agent decreases the effect of hydantoin
Pimecrolimus Pimecrolimus may enhance the adverse/toxic effect of immunosuppressants like bleomycin. This combination is contraindicated
Roflumilast Roflumilast may enhance the immunosuppressive effect of Immunosuppressants.The Canadian product monograph (Daxas brand) recommends avoiding concurrent use with immunosuppressants. U.S. prescribing information (Daliresp brand) does not include such a warning.
Tacrolimus Tacrolimus (Topical) may enhance the adverse/toxic effect of Immunosuppressants. Avoid use of tacrolimus ointment in patients receiving immunosuppressants.
Trastuzumab Trastuzumab may increase the risk of neutropenia and anemia. Monitor closely for signs and symptoms of adverse events.
Food Interactions Not Available

Targets


DNA ligase 1
Name DNA ligase 1
Gene Name LIG1
Pharmacological action unknown
Actions inhibitor
References
  • 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
DTHybrid score 1.8511
DNA
Name DNA
Gene Name Not Available
Pharmacological action yes
Actions cleavage
References
  • 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. - Pubmed
  • 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. Epub 2008 Aug 29. - Pubmed
  • 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. Epub 2008 Jul 3. - Pubmed
  • 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
DTHybrid score Not Available
DNA ligase 3
Name DNA ligase 3
Gene Name LIG3
Pharmacological action unknown
Actions inhibitor
References
  • 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
DTHybrid score 1.8511

Enzymes


Bleomycin hydrolase
Name Bleomycin hydrolase
Gene Name Not Available
Actions substrate
References
  • Lazo JS, Boland CJ, Schwartz PE: Bleomycin hydrolase activity and cytotoxicity in human tumors. Cancer Res. 1982 Oct;42(10):4026-31. - Pubmed
  • 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
DTHybrid score Not Available

Predictions


Id Partner name Gene Name Score
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