Bleomycin

Structural formula
	Structural formula of bleomycin A 2
General
Non-proprietary name	Bleomycin
Molecular formula	C 55 H 84 N 17 O 21 S 3 + (bleomycin A 2 ) ; C 55 H 84 N 20 O 21 S 2 (Bleomycin B 2 ) ;
External identifiers / databases
DrugBank	DB00290
Wikidata	Q415571
Drug information
ATC code	L01 DC01
properties
Molar mass	1415.56 g · mol -1 (bleomycin A 2 )
Melting point	200–204 ° C (bleomycin A 2 sulfate)
pK s value	7.3-7.7 (bleomycin A 2 )
solubility	20 mg / ml (bleomycin A 2 sulfate)
safety instructions
	Please note the exemption from the labeling requirement for drugs, medical devices, cosmetics, food and animal feed
GHS hazard labeling ; no classification available
	As far as possible and customary, SI units are used. Unless otherwise noted, the data given apply to standard conditions .

Bleomycin is a cytostatic effective drug which is used in the treatment of cancer ( chemotherapy ) and the so-called tumor antibiotics belongs. The antibiotic spectrum of activity of the glycopeptide is not used therapeutically.

The water-soluble salts bleomycin sulfate and hydrochloride are used pharmaceutically .

Origin and composition

Bleomycins are naturally produced by Streptomyces verticillus . Streptomycetes are a genus of actinobacteria . Bleomycin was discovered in 1962 by the Japanese scientist Hamao Umezawa .

The medicinal substance bleomycin is produced fermentatively in bacterial cultures and obtained from the culture filtrate by ion exchange absorption. It is essentially composed of two individual compounds from the bleomycin group: 55-70% of the dimethylsulfoniumaminopropyl derivative (= bleomycin A ₂ ) and 25-32 % of the agmatine derivative (= bleomycin B ₂ ) of bleomycic acid; the total content of bleomycin A ₂ + B ₂ is at least 85%.

pharmacology

In oncology , bleomycin is used as a cytostatic in combination with cisplatin and etoposide , among other things . Bleomycin complexes a divalent metal cation, predominantly Fe (II) . This complex is oxidized and activated by means of reactive oxygen species ( ROS ). The activated complex causes a radical abstraction of the 4'-H atom of a nucleotide in the small groove of the DNA, which results in a DNA strand break. This leads to the fragmentation of the DNA. Bleomycin also inhibits DNA-dependent DNA polymerase .

Bleomycin is rarely used in dermatology - usually in combination with salicylic acid - intralesionally as a wart remedy .

Side effects

A major side effect, which occurs in up to 18% of patients treated with bleomycin, is pulmonary fibrosis . Risk factors for developing bleomycin-induced pulmonary fibrosis are old age, a high dose of active ingredient, increased oxygen concentration in the inhaled air , irradiation of the chest (at the same time or later) and renal insufficiency . This side effect usually occurs after 1–6 months, but it can also occur more rarely acutely or not until much later than after 6 months.

Trade names

Monopreparations

Bleo-cell (D), Bleomedac (D), various generics (D, A, CH)

Individual evidence

↑ ^a ^b ^c Entry on Bleomycins. In: Römpp Online . Georg Thieme Verlag, accessed on June 27, 2019.
↑ This substance has either not yet been classified with regard to its hazardousness or a reliable and citable source has not yet been found.
↑ External identifiers or database links for bleomycin sulfate: CAS number: 9041-93-4, EC number: 232-925-2, ECHA InfoCard: 100.029.920 , PubChem : 72466 , ChemSpider : 17339341 , Wikidata : Q72533782 .
↑ External identifiers or database links for bleomycin hydrochloride: CAS number: 67763-87-5, EC number: 689-127-6, ECHA InfoCard: 100.215.902 , PubChem : 74219430 , ChemSpider : 21782093 , Wikidata : Q72447689 .
↑ Wissenschaft-Online-Lexika: Entry on "Bleomycine" in the Lexikon der Biochemie , accessed on October 5, 2011.
↑ H.-H. Frey, FR Althaus: Textbook of pharmacology and toxicology for veterinary medicine. P. 489, Georg Thieme Verlag, 2007, ISBN 978-3-8304-1070-6 .
↑ Dermatology: Warts - as they come, as they go , Deutsche Apothekerzeitung, 2003, No. 9, p. 40, February 23, 2003.
^ Heinrich Schmidt-Matthiesen , Gunther Bastert , Diethelm Wallwiener (eds.): Gynecological Oncology: Diagnostics, Therapy and Follow-up Care - on the basis of the AGO guidelines. 7th edition, p. 221, Schattauer Verlag, 2002, ISBN 978-3-7945-2182-1 .
↑ Red List, as of August 2009.
↑ AM comp. d. Switzerland, as of August 2009.
↑ AGES-PharmMed, as of August 2009.

[römpp-1] Entry on Bleomycins. In: Römpp Online . Georg Thieme Verlag, accessed on June 27, 2019.

[NV-2] This substance has either not yet been classified with regard to its hazardousness or a reliable and citable source has not yet been found.

[3] External identifiers or database links for bleomycin sulfate: CAS number: 9041-93-4, EC number: 232-925-2, ECHA InfoCard: 100.029.920 , PubChem : 72466 , ChemSpider : 17339341 , Wikidata : Q72533782 .

[4] External identifiers or database links for bleomycin hydrochloride: CAS number: 67763-87-5, EC number: 689-127-6, ECHA InfoCard: 100.215.902 , PubChem : 74219430 , ChemSpider : 21782093 , Wikidata : Q72447689 .

[5] Wissenschaft-Online-Lexika: Entry on "Bleomycine" in the Lexikon der Biochemie , accessed on October 5, 2011.

[6] H.-H. Frey, FR Althaus: Textbook of pharmacology and toxicology for veterinary medicine. P. 489, Georg Thieme Verlag, 2007, ISBN 978-3-8304-1070-6 .

[7] Dermatology: Warts - as they come, as they go , Deutsche Apothekerzeitung, 2003, No. 9, p. 40, February 23, 2003.

[8] Heinrich Schmidt-Matthiesen , Gunther Bastert , Diethelm Wallwiener (eds.): Gynecological Oncology: Diagnostics, Therapy and Follow-up Care - on the basis of the AGO guidelines. 7th edition, p. 221, Schattauer Verlag, 2002, ISBN 978-3-7945-2182-1 .

[9] Red List, as of August 2009.

[10] AM comp. d. Switzerland, as of August 2009.

[11] AGES-PharmMed, as of August 2009.