5-フルオロウラシル 化学特征,用处語,生産方式
外観
红色, 結晶～粉末
消融性
ジメチルホルムアミドに溶けやすく、水にやや溶けにくく、エタノールに溶けにくく、アセトンにほとんど溶けない。
解説
フルオロウラシル，化学式はC4II3FN2O2，核酸塩基ウラシルの５位の水素をフッ素原子で置換した誘導体で，代表英文的な抗癌剤の一つ。ウラシルをフッ素化すると得られる．颜色の結晶．分化点280～282 ℃．λmax 265～266 nm(ε 7070，pH 1.0)．水に難溶，DMFに易溶．抗悪性腫瘍剤で，消化器がん，乳がん治療薬として用される．LD50 226 mg/kg(マウス，経口)．融点約280℃。水に微溶，エタノールに難溶。腫瘍細胞内でDNA溶解を妨げて増殖を不许，またRNAに取り込まれて異常タンパク質を溶解させ，細胞を灭亡させる。乳癌や消化器癌などに用いられる。
用处
抗癌剤研讨用。
用处
人間と動物医療域の抗腫瘍剤(乳房と消化管)
用处
チミジル酸シンターゼを阻害
することにより DNA 分解阻害感化を示しま
す
用处
チミジル酸シンターゼを阻害
することにより DNA 分解阻害感化を示しま
す。
効能
抗悪性腫瘍薬, 代謝拮抗薬
商品名
5−FU (協和発酵キリン); 5−FU (協和発酵キリン); 5−FU (協和発酵キリン)
説明
5-Fluorouracil (5-FU) is a prodrug form of the thymidylate synthase inhibitor fluorodeoxyuridylate (FdUMP). It is also converted to the active metabolites FUTP and FdUTP, which induce RNA and DNA damage, respectively.
In vivo, 5-FU (15 mg/kg) when administered in combination with docetaxel reduces tumor growth in B88 and CAL 27 oral squamous cell carcinoma (OSCC) mouse xenograft models. Formulations containing 5-FU have been used in the treatment of colorectal, breast, gastric, and pancreatic cancers.
化学的特征
White or almost white, crystalline powder
利用
5-Fluorouracil is used as an antitumor agent in the treatment of anal, breast, colorectal, oesophageal, stomach, pancreatic and skin cancers. It finds application as a suicide inhibitor due to its irreversible inhibition of thymidylate synthase. It is also used in the treatment of actinic keratoses and bowen's disease. Further, it serves as a potent antineoplastic agent in clinical use. In addition to this, it acts as a DNA synthesis inhibitor.
適応症
Fluorouracil (5-fluorouracil, 5-fluorouracil, Efudex,
Adrucil) is a halogenated pyrimidine analogue that
must be activated metabolically. The active metabolite
that inhibits DNA synthesis is the deoxyribonucleotide
5-fluoro-2'deoxyuridine-S'-phosphate (FdUMP). 5-
Fluorouracil is selectively toxic to proliferating rather
than non-proliferating cells and is active in both the G1-
and S-phases. The target enzyme inhibited by 5-fluorouracilfluorouracil is thymidylate synthetase.
methylenetetrahydrofolate dihydrofolate
The carbon-donating cofactor for this reaction is
N
5,N
10 methylenetetrahydrofolate, which is converted
to dihydrofolate. The reduced folate cofactor occupies
an allosteric site on thymidylate synthetase, which allows
for the covalent binding of 5-FdUMP to the active
site of the enzyme.
普通的な説明
White to nearly white crystalline powder; practically odorless. Used as an anti neoplastic drug, chemosterilant for insects.
空気と水の反応
Insoluble in water.
反応プロフィール
5-Fluorouracil may be sensitive to prolonged exposure to light. Solutions discolor on storage. 5-Fluorouracil can react with oxidizing agents and strong bases. Incompatible with methotrexate sodium.
危険性
Questionable carcinogen.
安康ハザード
Minimum toxic dose in humans is approximately 450 mg/kg (total dose) over 30 days for the ingested drug. Intravenous minimum toxic dose in humans is a total dose of 6 mg/kg over three days. Depression of white blood cells occurred after intravenous administrative of a total dose of 480 mg/kg over 32 days. Occasional neuropathy and cardiac toxicity have been reported. Do not use during pregnancy. Patients with impaired hepatic or renal function, with a history of high-dose pelvic irradiation or previous use of alkylating agents should be treated with extreme caution. Patients with nutritional deficiencies and protein depletion have a reduced tolerance to 5-Fluorouracil.
火災危険
Emits very toxic fumes of flourides and nitrogen oxides when heated to decomposition. Avoid decomposing heat.
生物活性
Anticancer agent. Metabolized to form fluorodeoxyuridine monophosphate (FdUMP), fluorodeoxyuridine triphosphate (FdUTP) and fluorouridine (FUTP). FdUMP inhibits thymidylate reductase causing a reduction in dTMP synthesis. FUTP and FdUTP are misincorporated into RNA and DNA respectively.
感化機序
Another action proposed for 5-fluorouracil may involve
the incorporation of the nucleotide 5-fluorouridine
triphosphate (5-FUTP) into RNA. The cytotoxic
role of these “fraudulent” 5-fluorouracil-containing
RNAs is not well understood.
Several possible mechanisms of resistance to 5-fluorouracil
have been identified, including increased synthesis
of the target enzyme, altered affinity of thymidylate
synthetase for FdUMP, depletion of enzymes
(especially uridine kinase) that activate 5-fluorouracil
to nucleotides, an increase in the pool of the normal
metabolite deoxyuridylic acid (dUMP), and an increase
in the rate of catabolism of 5-fluorouracil.
The drug has been administered orally, but absorption
by this route is erratic. The plasma half-life of 5-
fluorouracil after intravenous injection is 10 to 20 minutes.
It readily enters CSF. Less than 20% of the parent
compound is excreted into the urine, the rest being
largely metabolized in the liver.
薬理学
Local inflammatory reactions characterized
by erythema, edema, crusting, burning, and pain are
common (and, some would argue, desirable) but may be
minimized by reduced frequency of application or use
in combination with a topical corticosteroid.
臨床応用
5-Fluorouracil (FU) is widely used in the treatment of a range of cancers including breast and cancers of the aerodigestive tract, but has had the greatest impact in colorectal cancer. 5-FU-based chemotherapy improves overall and disease-free survival of patients with resected stage III colorectal cancer. Nonetheless, response rates for 5-FU-based chemotherapy as a first-line treatment for advanced colorectal cancer are only between 10 and 15%. Combination of 5-FU with newer chemotherapies, such as irinotecan and oxaliplatin, has improved the response rates for advanced colorectal cancer to between 40 and 50%.
副感化
Patients who are genetically deficient in this enzyme will experience a more pronounced effect from this drug and are at significant risk for use-limiting toxicity. In general, women clear fluorouracil faster than men do. Dosage adjustments usually are not required in hepatic or renal dysfunction. Major toxicities are related to bone marrow depression, stomatitis/esophagopharyngitis, and potential GI ulceration. Nausea and vomiting are common. Solutions of fluorouracil are light sensitive, but discolored products that have been properly stored and protected from light are still safe to use.
宁静性プロファイル
Poison by ingestion,
intraperitoneal, subcutaneous, and
intravenous routes. Moderately toxic by
parented and rectal routes. Experimental
teratogenic and reproductive effects. Human
systemic effects: EKG changes, bone
marrow changes, cardiac, pulmonary, and
gastrointestinal effects. Human mutation
data reported. A human skin irritant.
Questionable carcinogen. When heated to decomposition it emits very toxic fumes of
Fand NOx.
職業ばく露
This material is used as an antineo plastic drug for cancer treatment and as a chemosterilant
for insects.
輸送方式
UN2811 Toxic solids, organic, n.o.s., Hazard
Class: 6.1; Labels: 6.1-Poisonous materials, Technical Name
Required.
和睦合性
Incompatible with oxidizers (chlorates,
nitrates, peroxides, permanganates, perchlorates, chlorine,
bromine, fluorine, etc.); contact may cause fires or explo sions. Keep away from alkaline materials, strong bases,
strong acids, oxoacids, epoxides, methotrexrate sodium,
sources of heat.
5-フルオロウラシル 下贱と下贱の製品情報
原资料
準備製品