Bleomycin hydrochloride
[CAS# 67763-87-5]

Identification

• Classification: API >> Antineoplastic agents >> Antibiotic antineoplastic agents
• Name: Bleomycin hydrochloride
• Synonyms: 3-[[2-[2-[2-[[(2S,3R)-2-[[(2S,3S,4R)-4-[[(2S,3R)-2-[[6-amino-2-[(1S)-3-amino-1-[[(2S)-2,3-diamino-3-oxopropyl]amino]-3-oxopropyl]-5-methylpyrimidine-4-carbonyl]amino]-3-[(2R,3S,4S,5S,6S)-3-[(2R,3S,4S,5R,6R)-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)propanoyl]amino]-3-hydroxy-2-methylpentanoyl]amino]-3-hydroxybutanoyl]amino]ethyl]-1,3-thiazol-4-yl]-1,3-thiazole-4-carbonyl]amino]propyl-dimethylsulfanium;hydrochloride
• Molecular Formula: C₅₀H₇₁N₁₆O₂₁S₂R.x(HCl)
• CAS Registry Number: 67763-87-5
• EC Number: 689-127-6
• SMILES: CC1=C(N=C(N=C1N)[C@H](CC(=O)N)NC[C@@H](C(=O)N)N)C(=O)N[C@@H]([C@H](C2=CN=CN2)O[C@H]3[C@H]([C@H]([C@@H]([C@@H](O3)CO)O)O)O[C@@H]4[C@H]([C@H]([C@@H]([C@H](O4)CO)O)OC(=O)N)O)C(=O)N[C@H](C)[C@H]([C@H](C)C(=O)N[C@@H]([C@@H](C)O)C(=O)NCCC5=NC(=CS5)C6=NC(=CS6)C(=O)NCCC[S+](C)C)O.Cl

Safety Data

• Hazard Symbols: GHS07 Warning
• Risk Statements: H302-H315-H319-H335
• Safety Statements: P280-P305+P351+P338

Hazard Classification

Hazard	Class	Category Code	Hazard Statement
Carcinogenicity	Carc.	2	H351

Discovery and Applications

Bleomycin hydrochloride is a glycopeptide antibiotic widely recognized for its clinical use as an antitumor agent. It is a member of the bleomycin family of compounds, originally isolated from the bacterium Streptomyces verticillus in the 1960s. The discovery of bleomycin marked a significant advancement in cancer chemotherapy due to its unique mechanism of action and effectiveness against various malignancies.

Chemically, bleomycin hydrochloride is a complex molecule composed of a mixture of closely related bleomycin peptides, characterized by a metal-binding domain, a DNA-binding region, and a carbohydrate moiety. The hydrochloride salt form enhances its solubility and stability, facilitating its administration in clinical settings.

The primary mechanism by which bleomycin exerts its antitumor effects is through binding to DNA and inducing strand breaks. This occurs via an oxygen- and metal ion-dependent process where bleomycin chelates metal ions, commonly iron, and generates reactive oxygen species that cause DNA scission. The resulting DNA damage leads to inhibition of DNA synthesis and cell death, particularly affecting rapidly dividing tumor cells.

Bleomycin hydrochloride has been extensively used in the treatment of various cancers, including Hodgkin's lymphoma, non-Hodgkin's lymphoma, testicular cancer, and certain types of squamous cell carcinomas. It is often employed as part of combination chemotherapy regimens, where its distinct mechanism complements other cytotoxic agents.

Beyond its antitumor activity, bleomycin has been utilized in clinical settings for its sclerosing properties in pleurodesis to treat pleural effusions. Its ability to induce fibrosis in the pleural space helps prevent recurrent fluid accumulation in patients with malignant or non-malignant effusions.

Despite its therapeutic benefits, bleomycin hydrochloride has notable side effects, the most significant being pulmonary toxicity. Bleomycin-induced lung injury can manifest as pneumonitis or pulmonary fibrosis, which limits the cumulative dose that can be safely administered. Monitoring and managing these adverse effects are critical components of clinical use.

In research, bleomycin has also been employed as a tool to study DNA damage and repair mechanisms due to its ability to induce specific DNA strand breaks. This has contributed to a broader understanding of cellular responses to genotoxic stress.

In summary, bleomycin hydrochloride is a clinically important glycopeptide antibiotic used primarily as a chemotherapeutic agent. Its discovery provided a new class of DNA-damaging drugs effective against various cancers. The compound's ability to induce DNA strand breaks underlies its antitumor activity, while its salt form ensures appropriate pharmacological properties for therapeutic use.

References

1974. Bleomycin: Clinical Pharmacology and Therapeutic Use. Cancer Chemotherapy Reports, 58(4).
PMID: 4136141

1991. Bleomycin-induced DNA damage and repair in human cells. Mutation Research/DNA Repair, 255(2).
DOI: 10.1016/0921-8777(91)90024-9

2018. Mechanisms of Bleomycin-Induced Lung Fibrosis. Frontiers in Pharmacology, 9.
DOI: 10.3389/fphar.2018.00957