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螺莫司汀

螺莫司汀用途

NCI172112 是一种经典的双功能烷化剂,是为了开发有效抗中枢神经系统肿瘤而合成的一种抗肿瘤剂。

螺莫司汀名称

[ CAS 号 ]:
56605-16-4

[ 中文名 ]:
螺莫司汀

[ 英文名 ]:
Spiromustine

[英文别名 ]:

Spirohydantoin mustard
Spiromustine
NCI172112

螺莫司汀生物活性

[ 描述 ]:

NCI172112 是一种经典的双功能烷化剂,是为了开发有效抗中枢神经系统肿瘤而合成的一种抗肿瘤剂。

[ 相关类别 ]:

信号通路 >> 其他 >> 其他

研究领域 >> 癌症

[体内研究]

NCI172112(螺乙内酰芥菜,SHM)可能作为跨越血脑屏障的载体[1]。测量给予[2-氯乙基-U-14C] NCI172112或[乙内酰脲-4-14C] NCI172112(3.13mg/kg.iv)后大鼠尿液和粪便中放射性的累积排泄。给药后4小时,用[乙内酰脲-14C] NCI172112处理的大鼠的尿中排出的放射性显着(P <0.005)大于[乙基-14C] NCI172112。然而,到24小时,用两种标记物质在尿液中回收约50％的剂量。粪便中放射性的清除是缓慢的,但是对于肾脏排泄,对于乙内酰脲-14C部分来说明显更大。在接受单次给予[乙内酰脲-14C] NCI172112的大鼠的呼出气中未发现放射性,并且在给予[乙基-14C] NCI172112后测量小于1％。 [14C] NCI172112给予胆管插管大鼠后4小时放射性肾清除率相似,乙基-14C为14.1±2.9和17.5±2.1％,乙内酰脲-14C为34.5±2.5和33.1±6.3％剂量分别为3.13和6.25 mg/kg后出现在尿液中的剂量。在给予[14 C] NCI172112(1mg/kg,iv)的狗中也观察到两种标记物的4小时尿排泄的差异。乙内酰脲-14C和乙基-14C消除的百分比分别为29.4±2.7％和17.2±3.5％(P <0.05)[2]。

[动物实验]

大鼠[2]雄性Sprague-Dawley大鼠（190-240g）用戊巴比妥（30mg / kg ip）轻度麻醉，并将溶于DMSO中的[14C] NCI172112（2μCi/大鼠，3.13mg / kg）注射到股骨中静脉。将动物单独饲养在玻璃代谢笼中，获取食物和水96小时，分别收集尿液和粪便。在96小时，用过量的戊巴比妥杀死大鼠，并将每个屠体在4体积％中均质化。用Waring搅拌机加水。药物溶液等分试样的放射性。用15mL磷光体通过液体闪烁计数测量和尿液。狗[2]雌性猎狐犬，体重15-20公斤，用戊巴比妥（30毫克/千克）麻醉，并在整个实验过程中使用戊巴比妥添加剂保持这种状态。通过插入股静脉的导管将1mL DMSO中的[14 C] NCI172112（50-60μCi，1mg / kg）给予狗。通过留置导管以1分钟至4小时的定时间隔从股动脉取出血液样品，并转移至在碎冰上冷却的肝素化管中。立即取出0.5mL等分试样并用3mL 2mL体积提取。冷甲苯。将剩余的血液离心，并用NCS消化0.5mL等分试样的血浆，用2mL体积提取。用甲苯稀释或用2mL 10％三氯乙酸稀释。从狗血的初始采样到提取或pptn的开始。血浆程序，经过8-14分钟。

[参考文献]

[1]. Brown TD, et al. A phase I trial of spirohydantoin mustard (NSC 172112) in patients with advanced cancer. J Clin Oncol. 1986 Aug;4(8):1270-6.

[2]. Plowman J, et al. The disposition of spirohydantoin mustard (NSC 172112) in rats and dogs. Xenobiotica. 1979 Jun;9(6):379-91.

[相关活性小分子]

螺莫司汀物理化学性质

[ 密度 ]:
1.29g/cm3

[ 熔点 ]:
125.5°C

[ 分子式 ]:
C₁₄H₂₃Cl₂N₃O₂

[ 分子量 ]:
336.25700

[ 精确质量 ]:
335.11700

[ PSA ]:
52.65000

[ LogP ]:
2.28740

[ 折射率 ]:
1.56

[ 储存条件 ]:
2-8℃

螺莫司汀毒性和生态

CHEMICAL IDENTIFICATION

RTECS NUMBER :: HM2508000

CHEMICAL NAME :: 1,3-Diazaspiro(4.5)decane-2,4-dione, 3-(2-(bis(2-chloroethyl)amino)ethyl)-

CAS REGISTRY NUMBER :: 56605-16-4

BEILSTEIN REFERENCE NO. :: 0757144

LAST UPDATED :: 199612

DATA ITEMS CITED :: 7

MOLECULAR FORMULA :: C14-H23-Cl2-N3-O2

MOLECULAR WEIGHT :: 336.30

HEALTH HAZARD DATA

ACUTE TOXICITY DATA

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Intravenous

SPECIES OBSERVED :: Human

DOSE/DURATION :: 243 ug/kg/3W-I

TOXIC EFFECTS :: Behavioral - hallucinations, distorted perceptions Gastrointestinal - hypermotility, diarrhea Gastrointestinal - nausea or vomiting

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Intravenous

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 9100 ug/kg

TOXIC EFFECTS :: Sense Organs and Special Senses (Eye) - chromodacryorrhea Behavioral - changes in motor activity (specific assay) Nutritional and Gross Metabolic - weight loss or decreased weight gain

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Intraperitoneal

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 33244 ug/kg

TOXIC EFFECTS :: Details of toxic effects not reported other than lethal dose value

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Intravenous

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 48280 ug/kg

TOXIC EFFECTS :: Skin and Appendages - hair Nutritional and Gross Metabolic - weight loss or decreased weight gain

TYPE OF TEST :: LDLo - Lowest published lethal dose

ROUTE OF EXPOSURE :: Intravenous

SPECIES OBSERVED :: Mammal - dog

DOSE/DURATION :: 3750 ug/kg

TOXIC EFFECTS :: Behavioral - somnolence (general depressed activity) Behavioral - food intake (animal) Nutritional and Gross Metabolic - body temperature decrease

MUTATION DATA

TYPE OF TEST :: Body fluid assay

TEST SYSTEM :: Rodent - mouse Bacteria - Salmonella typhimurium

DOSE/DURATION :: 60 mg/kg

REFERENCE :: BCPCA6 Biochemical Pharmacology. (Pergamon Press Inc., Maxwell House, Fairview Park, Elmsford, NY 10523) V.1- 1958- Volume(issue)/page/year: 32,523,1983