5-アザシチジン 化学特性,用途語,生産方法
外観
白色～わずかにうすい褐色、結晶～粉末
溶解性
水に溶け、エタノール及びアセトンにほとんど溶けない。
用途
DNA メチル化阻害作用及びタ
ンパク合成阻害作用を示します。
用途
医薬、医薬中間体、抗がん剤
効能
抗悪性腫瘍薬, 代謝拮抗薬
商品名
ビダーザ (日本新薬)
使用上の注意
不活性ガス封入
説明
5-Azacytidine is an analog of the nucleoside cytidine which can be incorporated into DNA and RNA. 5-Azacytidine acts as an epigenetic modifier by incorporating into DNA where it irreversibly binds to DNA methyltransferases, thus inhibiting their activity.
Azacitidine is an antineoplastic agent launched for the treatment of myelodysplastic syndrome (MDS). MDS is a group of closely related diseases caused by abnormal blood-forming stem cells of the bone marrow. Azacitidine is indicated for the treatment of all five subtypes of MDS, which consist of refractory anemia, refractory anemia with ringed sideroblasts, refractory anemia with excess blasts, refractory anemia with excess blasts in transformation, and chronic myelomonocytic leukemia.
化学的特性
White crystalline solid or powder. Soluble in dimethyl sulfoxide, slightly soluble in ethanol:water (50:50), propylene glycol, polyethylene glycol; slightly soluble in water, saturated octanol aqueous solution, 5% glucose injection, N-methyl-2-pyrrolidone, 0.9% sodium chloride injection and 5% polysorbate 80 aqueous solution; insoluble in acetone, ethanol and methyl ethyl ketone.
使用
5-Azacytidine, its incorporation into RNA alters RNA synthesis and processing, and results in inhibition of protein synthesis. It has been used as a cancer chemotherapeutic agent. It is a powerful bacteriostatic, antitumor, and mutagenic agent; it also exhibits immunosuppressive, antimitotic, radioprotective, and virostatic effects.
定義
ChEBI: A N-glycosyl-1,3,5-triazine that is 4-amino-1,3,5-triazin-2(1H)-one substituted by a beta-D-ribofuranosyl residue via a N-glycosidic linkage.
生物学の機能
Azacitidine is given subcutaneously for the treatment of myelodysplastic syndrome, and serum levels generally are maximized within 30 minutes. The parent drug and its metabolites are excreted in the urine. Azacitidine is carcinogenic and teratogenic in rodents, and leukopenia, thrombocytopenia, and neutropenia are the most common reasons for drug discontinuation or dosage reduction.
一般的な説明
White crystalline powder.
空気と水の反応
Slightly water soluble. Unstable in solution.
反応プロフィール
5-Azacytidine is sensitive to light (may discolor). 5-Azacytidine is sensitive to oxidation. 5-Azacytidine is unstable in solution. 5-Azacytidine undergoes hydrolysis in aqueous buffers. 5-Azacytidine is incompatible with strong oxidizers.
火災危険
Flash point data for 5-Azacytidine are not available; however, 5-Azacytidine is probably combustible.
生物活性
DNA methyltransferase inhibitor. Incorporates into DNA forming covalent adducts with cellular DNMT1, depleting enzyme activity. Induces demethylation and reactivation of silenced genes. Improves the efficiency of reprogramming of stem cells.
安全性プロファイル
Confirmed carcinogen
with experimental carcinogenic,
neoplastigenic, tumorigenic data. Poison by
ingestion, intravenous, and intraperitoneal
routes. Human systemic effects by
intravenous route: nausea, vomiting and
dlarrhea, reduction in white cell count
(luekopenia and agranulocytosis). An
experimental teratogen. Other experimental
reproductive effects. Human mutation data
reported. A skin irritant. When heated to
decomposition it emits toxic fumes of NOx.
発がん性
Azacitidine is reasonably anticipated to be a human carcinogen based on sufficient evidence of carcinogenicity from studies in experimental animals.
輸送方法
UN3249 Medicine, solid, toxic, n.o.s., Hazard
Class: 6.1; Labels: 6.1-Poisonous materials.
不和合性
Azacitidine is Incompatible with oxidizers
(chlorates, nitrates, peroxides, permanganates, perchlorates,
chlorine, bromine, fluorine, etc.); contact may cause
fires or explosions. Keep away from alkaline materials,
strong bases, strong acids, oxoacids, epoxides. Contact with
alkali metals, nitrides, and strong reducing agents such as
hydrides may form flammable and/or toxic gases. May react
with anhydrides forming acids and esters, generating noticeable
heat, and also with oxoacids and carboxylic acids to
form esters plus water, but the heat of reaction in the latter
case typically is low. Keep away from isocyanates and
epoxides; may initiate their polymerization. Azacitidine is
sensitive to light and oxidation and unstable in solution. It
undergoes hydrolysis in aqueous buffers.
廃棄物の処理
It is inappropriate and possibly
dangerous to the environment to dispose of expired or
waste drugs and pharmaceuticals by flushing them down
the toilet or discarding them to the trash. Household quantities
of expired or waste pharmaceuticals may be mixed
with wet cat litter or coffee grounds, double-bagged in
plastic, discard in trash. Larger quantities shall carefully
take into consideration applicable DEA, EPA, and FDA
regulations. If possible return the pharmaceutical to the
manufacturer for proper disposal being careful to properly
label and securely package the material. Alternatively, the
waste pharmaceutical shall be labeled, securely packaged
and transported by a state licensed medical waste contractor
to dispose by burial in a licensed hazardous or toxic waste
landfill or incinerator.
5-アザシチジン 上流と下流の製品情報
原材料
準備製品