| Identification | Back Directory | [Name]
Bleomycin | [CAS]
11056-06-7 | [Synonyms]
BLM
BLEO
BLEXANE
Bleocin
BLENOXANE
bleomicin
Bleomycin
Bleocinbase
DNA helicase
Bleo
Bleocin
RecQ-like type 2
BLEOMYCIN SULPHATE
RecQ protein-like 3
Bleomycin (usan 8ci9ci)
BleoMycin sulphate(Mycin series)
Bleomycin (base and/or unspecified salts)
BLEOMYCIN SULFATE, STREPTOMYCES VERTICILLUS
Anti-Bloom Syndrome, N-Terminal antibody produced in rabbit
N1-(3-(dimethylsulfonio)propyl)bleomycinamide) (Bleomycin A2)
4-(2,4-Dichloro-5-methoxyphenylamino)-6-methoxy-7-(3-(4-methylpiperazin-1-yl)propoxy)quinoline-3-carbonitrile
3-[[2-[2-[2-[2-[4-[2-[6-Amino-2-[1-(2-amino-2-carbamoyl-ethyl)amino-2-carbamoyl-ethyl]-5-methyl-pyrimidin-4-yl]carbonylamino-3-[3-[4-carbamoyloxy-3,5-dihydroxy-6-(hydroxymethyl)tetrahydropyran-2-yl]oxy-4,5-dihydroxy-6-(hydroxymethyl)tetrahydropyran-2-yl]o
3-[[2-[2-[2-[[2-[[4-[[2-[[6-Amino-2-[3-amino-1-[(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-(3H-imidazol-4-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 hydrogen sulfate
3-[[2-[2-[2-[[(2S,3R)-2-[[(2S,3S,4R)-4-[[(2S)-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-(3H-imidazol-4-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 | [EINECS(EC#)]
232-925-2 | [Molecular Formula]
C110H168N34O46S7 | [MDL Number]
MFCD00070310 | [MOL File]
11056-06-7.mol | [Molecular Weight]
2927.17 |
| Chemical Properties | Back Directory | [Definition]
A species of
bleomycin noted for its adverse pulmonary effects
in humans. It is a complex of related glycopeptide
antibiotics from Streptomyces verticillus consisting
of bleomycin A2 and B2.
| [Appearance]
colourless or light yellow powder | [storage temp. ]
2-8°C
| [solubility ]
H2O: 20 mg/mL
| [form ]
powder
| [color ]
white
| [IARC]
2B (Vol. 26, Sup 7) 1987, 1 (Vol. 76, 100A) 2012 | [EPA Substance Registry System]
Bleomycin(11056-06-7) |
| Hazard Information | Back Directory | [Chemical Properties]
colourless or light yellow powder | [General Description]
Colorless or yellowish powder. Possible bluish color depending on copper content. | [Air & Water Reactions]
Water soluble | [Fire Hazard]
Flash point data for Bleomycin are not available. Bleomycin is probably nonflammable. | [Hazard]
Possible carcinogen. | [Description]
Bleomycin is a complex of no less than 16 glycopeptide antibiotics made from the family Streptomyces verticilus, which have different R groups. Bleomycines exhibit
antitumor, antiviral, and antibacterial activity. When bound to DNA, they disturb the spiraling of both single and double strands of DNA. To a lesser degree, they inhibit RNA and
protein synthesis. It is administered both intravenously and intramuscularly. | [Originator]
Bleomycin
Hydrochloride,Nippon Kayaku, Co.,Japan | [Uses]
Antineoplastic for solid tumors.
| [Uses]
Bleomycin sulfate USP (Blenoxane)is used to traet squamous cell carcinoma of head, neck, esophagus, skin, GU tract; testicular tumor; Hodgkin’s lymphomas. | [Uses]
It is used for lymphomas, carcinomas, and sarcomas. | [Indications]
The bleomycins are a group of glycopeptides that are
isolated from Streptomyces verticillus. The clinical
preparation, bleomycin sulfate (Blenoxane), is a mixture
of several components. Bleomycin binds to DNA,
in part through an intercalation mechanism, without
markedly altering the secondary structure of the nucleic
acid. The drug produces both single- and double-strand
scission and fragmentation of DNA. It is thought that
the bleomycins, which are avid metal-chelating agents,
form a bleomycin–Fe ++ complex that can donate electrons
to molecular oxygen, thus forming the superoxide
and hydroxyl free radicals. It is these highly reactive intermediates
that attack DNA and produce DNA strand
breakage and maximum cytotoxicity in the late G2 and
early M-phases of the cell cycle. | [Manufacturing Process]
To a medium having a composition of 6.4 % of millet jelly, 0.5 % of glucose,
3.5 % of soybean powder, 0.75 % of corn steep liquor, 0.3 % of sodium
chloride, 0.1 % of potassium secondary phosphate, 0.05 % of zinc sulfate,
0.01 % of copper sulfate, 0.2 % of sodium nitrate and 0.01 % of Toho No. 1
(trade name for a surface active agent composed of polyoxyethylene
manufactured by Toho Chemical Industry Co. Ltd., Japan) was added 3-aminopropyl-
dimethylsulfonium bromide hydrobromate in a proportion of 0.4 mg/ml
to adjust the pH of the medium to 6.5.
Each 100 ml of the thus treated medium was separately charged into a
Sakaguchi flask and was then sterilized. Subsequently, Streptomyces
verticillus (ATCC No. 15003) was inoculated in the medium and was cultured
at 27°C for 8 days with stirring at 130 r.p.m. Thereafter, the culture liquors
(4.5 L) were collected and filtered to obtain 3.0 L of a filtrate (potency 38.8
mg/ml, total potency 416.4 mg). This culture filtrate was passed through and
adsorbed on a column packed with 200 ml of Amberlite IRC-50 and was
washed with water and was eluted with 0.5 N hydrochloric acid. 1.0 L of the
eluate was neutralized, was passed through and adsorbed on a column packed
with 100 ml of active carbon, was washed and was then eluted by use of a
1:1 (by volume) mixture of acetone - 0.02 N aqueous hydrochloric acid
solution, and fractions active to Mycobacterium 607 were collected and
concentrated to dryness. The resulting residue was dissolved in 5 ml of an 80
% aqueous methanol solution and was charged into a column packed with 30
ml of neutral alumina, followed by elution with an 80 % aqueous methanol
solution. Subsequently, bleomycin-containing fractions were collected and
concentrated to dryness to obtain 195 mg of bleomycin hydrochloride
(potency 650.7 mcg/mg, total potency 172 mg). The yield from the culture
filtrate was 30.5 %. | [Brand name]
Blenoxane (Bristol-Myers Squibb). | [Therapeutic Function]
Antibiotic | [Pharmaceutical Applications]
The drug Bleomycin (BLM) is successfully used as an anticancer agent, and is known to cause fragmentation
of the DNA. The drug is used for the treatment of testicular cancer, non-Hodgkin’s lymphoma, Hodgkin’s
lymphoma and cancers of the head and neck area (Cancer research UK). The name Bleomycin describes a
family of water-soluble antibiotics that can be isolated from the bacterium Streptomyces verticillus. All family
members contain the same core structure, a sulfur-containing polypeptide chain, and are only differentiated
by a small side group and the sugar moiety.
BLM was discovered 1966 by Umezawa et al. when they screened the filtrate of S. verticillus for cytotoxic
activity. The therapeutically active forms of BLM are BLM A2
and B2, which differ only in the side chain. BLM is believed to exhibit its anticancer activity by DNA degradation, a process that is dependent on
the presence of molecular oxygen, and the binding of a metal to BLM to form the so-called ‘activated BLM
complex’.
The structure of BLM consists of several biologically important units, each contributing to its anticancer
activity. Two structural units of importance to highlight are the metal-binding site and the DNA-binding
site. It is believed that the intercalation of DNA by BLM occurs via the C-terminus, which contains two
thiazole rings and the positively charged sulfonium salt. The positive charges of the sulfur atom can interact
with the negatively charged phosphate backbones of the DNA. The metal-binding site can be found at the
N-terminus and contains deprotonated amide and histidine groups. The metal is coordinated in a square planar
complex, where a primary amine group occupies the axial position. It can coordinate to a variety of
metals such as Cu2+, Co2+, Zn2+ and Fe2+, but it shows the highest binding affinity to Fe2+. The metal
chelation and subsequent activation of molecular oxygen is crucial to the antiproliferative activity of BLM.
The carbohydrate core seems to be less involved in the direct anticancer activity. Nevertheless, it has been
suggested that it regulates the cellular uptake and indirectly regulates the anticancer activity. | [Mechanism of action]
Bleomycin is poorly absorbed orally, but it can be
given by various parenteral routes. Its plasma half-life is
not affected by renal dysfunction as long as creatinine
clearance is greater than 35 mL/minute.
Bleomycin hydrolase, which inactivates bleomycin,
is an enzyme that is abundant in liver and kidney but
virtually absent in lungs and skin; the latter two organs
are the major targets of bleomycin toxicity. It is thought
that bleomycin-induced dermal and pulmonary toxicities
are related to the persistence of relatively high local
concentrations of active drug. | [Clinical Use]
Bleomycin, in combination with cisplatin or etoposide,
is important as part of the potentially curative
combination chemotherapy of advanced testicular carcinomas.
Bleomycin is used in some standard regimens
for the treatment of Hodgkin’s and non-Hodgkin’s lymphomas,
and it is useful against squamous cell carcinomas
of the head and neck, cervix, and skin. | [Side effects]
A potentially fatal lung toxicity occurs in 10 to 20%
of patients receiving bleomycin. Patients particularly at
risk are those who are over 70 years of age and have
had radiation therapy to the chest. Rarely, bleomycin
also may cause allergic pneumonitis. Bleomycin skin
toxicity is manifested by hyperpigmentation, erythematosus
rashes, and thickening of the skin over the
dorsum of the hands and at dermal pressure points,
such as the elbows. Many patients develop a low-grade
transient fever within 24 hours of receiving bleomycin.
Less common adverse effects include mucositis, alopecia,
headache, nausea, and arteritis of the distal extremities. | [Drug interactions]
Potentially hazardous interactions with other drugs
Antipsychotics: avoid clozapine, increased risk of
agranulocytosis.
Cytotoxics: increased pulmonary toxicity with
cisplatin and brentuximab, avoid with brentuximab;
in combination with vinca alkaloids can lead to
Raynaud’s syndrome and peripheral ischaemia.
Live vaccines: avoid concomitant use. | [Metabolism]
The mechanism for bio-transformation is not yet fully
known. Inactivation takes place during enzymatic
breakdown by bleomycin hydrolase, primarily in plasma,
liver and other organs and, to a much lesser degree, in skin
and lungs.
About 60-70% of the administered drug is excreted
unchanged in the urine, probably by glomerular filtration.
Approximately 50% is recovered in the urine in the
24 hours following an IV or IM injection. The rate of
excretion, therefore, is highly influenced by renal function;
concentrations in plasma are greatly elevated if usual
doses are given to patients with renal impairment with
only up to 20% excreted in 24 hours. |
|
| Company Name: |
LGM Pharma
|
| Tel: |
1-(800)-881-8210 |
| Website: |
www.lgmpharma.com |
| Company Name: |
BEST-REAGENT
|
| Tel: |
400-1166-196 18981987031 |
| Website: |
http://www.hx-r.com/ |
| Company Name: |
BOC Sciences
|
| Tel: |
1-631-485-4226; 16314854226 |
| Website: |
https://www.bocsci.com |
|