ブレオマイシン

MSDS Information

• 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

ブレオマイシン 化学特性,用途語,生産方法

• 解説

  Streptomyces verticillusの生産する抗生物質．Fe(II)と酸素と複合体を形成したブレオマイシンは，還元によってブレオマイシン-Fe(III)-HO₂^－型となって活性化され，一本鎖DNAを切断する．ブレオマイシンを投与したマウスでは皮膚で高いブレオマイシン濃度が観察されるが，これは他の臓器に比べてブレオマイシンが皮膚で分解されにくいからである．このため，ブレオマイシンはとくに扁平上皮がんに対して有効な制がん剤である．

• 用途

  ブレオマイシン系抗生物質DNA合成阻害およびDNA鎖切断により抗がん作用を示す

• 効能

  抗生物質, 抗悪性腫瘍薬

• 説明

  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.

• 使用

  Bleomycin sulfate USP (Blenoxane)is used to traet squamous cell carcinoma of head, neck, esophagus, skin, GU tract; testicular tumor; Hodgkin’s lymphomas.

• 適応症

  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.

• 定義

  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.

• 一般的な説明

  Bleomycin is a glycopeptide antibiotic complex isolatedfrom Streptomyces verticillus initially by Umezawa.Atleast 13 different fractions of bleomycin have been isolatedwith the clinically used product (Blenoxane) being a mixtureof predominantly A2₂ (55%–70%) and B₂ (25%–32%)fractions.Of these fractions, A₂ appears to possessthe greatest antineoplastic activity. Copper is found inthe naturally occurring material, and its removal is importantfor the material used clinically because it significantlyreduces activity.
  Bleomycin is notable for its lack of myelotoxicity, andthis allows it to be combined with other myelosuppressantswithout a resulting additive effect. The acute toxicities seenwith bleomycin are erythema (reddening of the skin), hyperpigmentation(skin darkening) found predominately on theextremities, and pulmonary toxicity. The pulmonary toxicitymay first occur as pneumonitis (inflammation of lung tissue),which normally responds to glucocorticosteroid therapy.Chronic pulmonary toxicity is expressed as pulmonaryfibrosis, which is irreversible and limits utility of the agent.

• 空気と水の反応

  Water soluble

• 危険性

  Possible carcinogen.

• 火災危険

  Flash point data for Bleomycin are not available. Bleomycin is probably nonflammable.

• 作用機序

  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.

• 臨床応用

  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.

• 副作用

  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.

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11056-06-7, ブレオマイシン キーワード