11056-06-7 Usage
Uses
Used in Oncology:
Bleomycin is used as an antineoplastic agent for the treatment of various types of cancer, including lymphomas, carcinomas, and sarcomas. It is particularly effective against squamous cell carcinoma of the head, neck, esophagus, skin, and genitourinary (GU) tract, as well as testicular tumors and Hodgkin's lymphomas.
Used in Pharmaceutical Industry:
Bleomycin sulfate USP (Blenoxane) is used in the pharmaceutical industry for the development and production of anticancer drugs, specifically for solid tumors. Its unique properties and lack of myelotoxicity make it a valuable component in combination therapies with other myelosuppressants.
Originator
Bleomycin
Hydrochloride,Nippon Kayaku, Co.,Japan
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 %.
Therapeutic Function
Antibiotic
Air & Water Reactions
Water soluble
Hazard
Possible carcinogen.
Fire Hazard
Flash point data for Bleomycin are not available. Bleomycin is probably nonflammable.
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.
Check Digit Verification of cas no
The CAS Registry Mumber 11056-06-7 includes 8 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 5 digits, 1,1,0,5 and 6 respectively; the second part has 2 digits, 0 and 6 respectively.
Calculate Digit Verification of CAS Registry Number 11056-06:
(7*1)+(6*1)+(5*0)+(4*5)+(3*6)+(2*0)+(1*6)=57
57 % 10 = 7
So 11056-06-7 is a valid CAS Registry Number.
InChI:InChI=1/C55H83N17O21S3/c1-20-33(69-46(72-44(20)58)25(12-31(57)76)64-13-24(56)45(59)82)50(86)71-35(41(26-14-61-19-65-26)91-54-43(39(80)37(78)29(15-73)90-54)92-53-40(81)42(93-55(60)88)38(79)30(16-74)89-53)51(87)66-22(3)36(77)21(2)47(83)70-34(23(4)75)49(85)63-10-8-32-67-28(18-94-32)52-68-27(17-95-52)48(84)62-9-7-11-96(5)6/h14,17-19,21-25,29-30,34-43,53-54,64,73-75,77-81H,7-13,15-16,56H2,1-6H3,(H13-,57,58,59,60,61,62,63,65,66,69,70,71,72,76,82,83,84,85,86,87,88)/p+1/t21-,22+,23+,24-,25-,29?,30?,34-,35-,36-,37?,38?,39?,40?,41-,42?,43?,53?,54?/m0/s1
11056-06-7Relevant articles and documents
THERAPEUTIC FOR HEPATIC CANCER
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, (2011/02/18)
A novel pharmaceutical composition for treating or preventing hepatocellular carcinoma and a method of treatment are provided. A pharmaceutical composition for treating or preventing liver cancer is obtained by combining a chemotherapeutic agent with an anti-glypican 3 antibody. Also disclosed is a pharmaceutical composition for treating or preventing liver cancer which comprises as an active ingredient an anti-glypican 3 antibody for use in combination with a chemotherapeutic agent, or which comprises as an active ingredient a chemotherapeutic agent for use in combination with an anti-glypican 3 antibody. Using the chemotherapeutic agent and the anti-glypican 3 antibody in combination yields better therapeutic effects than using the chemotherapeutic agent alone, and mitigates side effects that arise from liver cancer treatment with the chemotherapeutic agent.
Anti-Claudin 3 Monoclonal Antibody and Treatment and Diagnosis of Cancer Using the Same
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, (2010/05/13)
Monoclonal antibodies that bind specifically to Claudin 3 expressed on cell surface are provided. The antibodies of the present invention are useful for diagnosis of cancers that have enhanced expression of Claudin 3, such as ovarian cancer, prostate cancer, breast cancer, uterine cancer, liver cancer, lung cancer, pancreatic cancer, stomach cancer, bladder cancer, and colon cancer. The present invention provides monoclonal antibodies showing cytotoxic effects against cells of these cancers. Methods for inducing cell injury in Claudin 3-expressing cells and methods for suppressing proliferation of Claudin 3-expressing cells by contacting Claudin 3-expressing cells with a Claudin 3-binding antibody are disclosed. The present application also discloses methods for diagnosis or treatment of cancers.
Medicines for treating tumoral pathologies containing the ro5-4864 compound and an apoptosis-inducing agent
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, (2008/06/13)
The invention concerns the use of Ro5-4864, and compounds derived therefrom, for preparing medicines for treating tumoral pathologies. The invention also concerns said compounds combined with an apoptosis-inducing agent, as combination products for simultaneous, separate or prolonged use, in cancer therapy.
Compositions containing piperine
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, (2008/06/13)
A pharmaceutical composition having increased bioavailability characterized by piperine of the formula STR1 and a drug for treating a disease or condition of the human cardiovascular system, central nervous system, gastrointestinal tract, respiratory tract, endocrine system, genito urinary tract or haemopoietic system.
Compositions containing piperine
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, (2008/06/13)
A pharmaceutical composition having increased bioavailability characterized by piperine of the formula and a drug for treating a disease or condition of the human cardiovascular system, central nervous system, gastrointestinal tract, respiratory tract, endocrine system, genito urinary tract or haemopoietic system.
Amino acid and hydroxyamino acid transporter compounds for therapeutic applications, process and use
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, (2008/06/13)
Amino acid and hydroxyamino acid transporter compounds are provided, in which an amino acid or hydroxyamino acid as a carrier is linked via an ester linkage to a therapeutic compound, and having one of the general formulae: in which AA represents the amino acid or hydroxyamino acid, HAA represents the hydroxyamino acid, and Z1 and Z2 represent a therapeutic compound, or a linking compound attached to COOH or OH of the hydroxyamino acid and to the therapeutic compound, as well as a process for preparing the same, and a process for administration of the same to animals, to obtain the benefit of the therapeutic effect of the therapeutic compound.
Method of treating nausea and vomiting with certain substituted-phenylalkylamino (and aminoacid) derivatives and other serotonin depleting agents
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, (2008/06/13)
A method for the treatment of emesis in a mammal, which method comprises administering to said mammal an emesis inhibiting amount of a compound which depletes serotonin in the brain of mammals; among which are compounds having the formula: STR1 wherein, R is selected from hydrogen, loweralkyl, trifluoromethyl, carboxyl, or loweralkoxycarbonyl; R1 and R2 are hydrogen or loweralkyl; Z is trifluoromethyl or halogen; the optical isomers and pharmaceutically acceptable salts thereof; two of the preferred compounds of the invention are fenfluramine and norfenfluramine.
