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(+-)-A-甲基-4-羧基苯糖胶

(+-)-A-甲基-4-羧基苯糖胶用途

Melphalan 是一种有效的 DNA 烷化剂 (DNA alkylator),具有抗肿瘤活性。

(+-)-A-甲基-4-羧基苯糖胶名称

[ CAS 号 ]:
148-82-3

[ 中文名 ]:
美法仑

[ 英文名 ]:
melphalan

[中文别名 ]:

马法兰

[英文别名 ]:

4-[Bis(2-chloroethyl)amino]-L-phenylalanine
L-3-[p-[Bis(2-chloroethyl)amino]phenyl]alanine
melphalan
L-Phenylalanine, 4-(bis(2-chloroethyl)amino)-
MFCD00057717
L-Phenylalanine, 4-[bis(2-chloroethyl)amino]-
Sarcoclorin
3025 C.B.
L-Phenylalanine mustard
EINECS 205-726-3

(+-)-A-甲基-4-羧基苯糖胶生物活性

[ 描述 ]:

Melphalan 是一种有效的 DNA 烷化剂 (DNA alkylator),具有抗肿瘤活性。

[ 相关类别 ]:

信号通路 >> 细胞周期/DNA损伤 >> DNA烷基化剂/交联剂

研究领域 >> 癌症

[ 靶点 ]

DNA Alkylator/Crosslinker[1]

[体外研究]

美法仑是一种DNA烷化剂,用于多发性骨髓瘤[1]。美法仑-DNA加合物可在培养细胞和实体肿瘤组织中可视化[3]。

[体内研究]

美法仑(12 mg/kg,ip)可增加SD大鼠的热量药理活性[2]。

[细胞实验]

通过MTT测定法测定美法仑的细胞毒性。将细胞以每孔1000个细胞接种于96孔微量滴定板的100μL培养基中，在37℃，5％CO 2下2天后每孔获得约4000个细胞。然后，洗涤细胞并在37℃，5％CO 2下暴露于0,10,25,50,100,250或500μM美法仑1小时。为了控制盐酸的细胞毒性，将美法仑的溶剂，细胞也暴露于盐酸，其浓度调节至最高浓度的美法仑（500μM）。处理后，用培养基洗涤细胞两次，加入100μL新鲜培养基。在暴露于美法仑后的第二天，加入另外的100μL新鲜培养基。再过2天后，除去培养基并加入200μL新鲜培养基。在处理后第4天，除去培养基，并将细胞与100μL新鲜培养基和10μLMTT标记试剂一起温育4小时。随后，加入100μL增溶溶液（10％（v / v）的0.01M HCl溶液）。孵育过夜后，通过微量滴定板读数器测量590nm处的吸光度[3]。

[动物实验]

大鼠[2]根据腹膜内温度将20只大鼠随机分成两组。常温（NT）组接受腹膜内化疗，腹膜内温度保持在32.5和34.5℃之间，高温（HT）组接受腹膜内化疗，腹膜内温度保持在41.5和42.5℃之间。在给药前立即将12mg / kg剂量的美法仑稀释在150mL 0.9％NaCl溶液中。使用封闭的灌注系统。灌注液在恒温调节的水浴中在管线圈中加热，并用滚子泵以80mL / min的速率注入腹膜腔90分钟。腹部的节律性按摩用于促进腹膜腔内均匀的热分布。当在腹膜腔内达到实验的适当温度时，将美法仑加入到储库中的灌注液中。对于每只动物，在化疗开始后5,15,30,60和90分钟收集0.5mL腹膜液和0.5mL血液。每次采血后，用0.2mL肝素化盐水冲洗静脉导管。在该过程结束时，杀死大鼠并取出组织样品[2]。

[参考文献]

[1]. BLUMBERG BS, et al. AN ALKYLATING AGENT FOR MULTIPLE MYELOMA: MELPHALAN. JAMA. 1965 Feb 15;191:547-9.

[2]. Glehen O, et al. Hyperthermia modifies pharmacokinetics and tissue distribution of intraperitoneal melphalan in a rat model. Cancer Chemother Pharmacol. 2004 Jul;54(1):79-84.

[3]. Rothbarth J, et al. Immunohistochemical detection of melphalan-DNA adducts in colon cancer cells in vitro and human colorectal liver tumours in vivo. Biochem Pharmacol. 2004 May 1;67(9):1771-8.

[相关活性小分子]

(+-)-A-甲基-4-羧基苯糖胶物理化学性质

[ 密度 ]:
1.3±0.1 g/cm3

[ 沸点 ]:
473.1±45.0 °C at 760 mmHg

[ 熔点 ]:
~180 °C

[ 分子式 ]:
C₁₃H₁₈Cl₂N₂O₂

[ 分子量 ]:
305.200

[ 闪点 ]:
239.9±28.7 °C

[ 精确质量 ]:
304.074524

[ PSA ]:
66.56000

[ LogP ]:
1.79

[ 外观性状 ]:
结晶固体

[ 蒸汽压 ]:
0.0±1.2 mmHg at 25°C

[ 折射率 ]:
1.597

[ 储存条件 ]:
-20?C Freezer

[ 水溶解性 ]:
95% ethanol and 1 drop 6 N HCl: 0.05 g/mL, clear | <0.1 g/100 mL at 22 ºC

(+-)-A-甲基-4-羧基苯糖胶毒性和生态

CHEMICAL IDENTIFICATION

RTECS NUMBER :: AY3675000

CHEMICAL NAME :: Alanine, 3-(p-(bis(2-chloroethyl)amino)phenyl)-, L-

CAS REGISTRY NUMBER :: 148-82-3

BEILSTEIN REFERENCE NO. :: 2816456

LAST UPDATED :: 199712

DATA ITEMS CITED :: 95

MOLECULAR FORMULA :: C13-H18-Cl2-N2-O2

MOLECULAR WEIGHT :: 305.23

WISWESSER LINE NOTATION :: QVYZ1R DN2G2G -L

HEALTH HAZARD DATA

ACUTE TOXICITY DATA

TYPE OF TEST :: Rinsed with water

ROUTE OF EXPOSURE :: Administration onto the skin

SPECIES OBSERVED :: Rodent - rabbit

TYPE OF TEST :: Standard Draize test

ROUTE OF EXPOSURE :: Administration onto the skin

SPECIES OBSERVED :: Rodent - rabbit

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Human

DOSE/DURATION :: 700 mg/kg/7D

TOXIC EFFECTS :: Gastrointestinal - nausea or vomiting

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Human

DOSE/DURATION :: 1200 ug/kg/5D-I

TOXIC EFFECTS :: Gastrointestinal - nausea or vomiting

TYPE OF TEST :: LDLo - Lowest published lethal dose

ROUTE OF EXPOSURE :: Intravenous

SPECIES OBSERVED :: Human - child

DOSE/DURATION :: 4500 mg/kg

TOXIC EFFECTS :: Behavioral - anorexia (human) Gastrointestinal - hypermotility, diarrhea Blood - agranulocytosis

TYPE OF TEST :: LDLo - Lowest published lethal dose

ROUTE OF EXPOSURE :: Intravenous

SPECIES OBSERVED :: Human - man

DOSE/DURATION :: 8140 mg/kg

TOXIC EFFECTS :: Behavioral - anorexia (human) Gastrointestinal - hypermotility, diarrhea Blood - agranulocytosis

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Intravenous

SPECIES OBSERVED :: Human - infant

DOSE/DURATION :: 28 mg/kg

TOXIC EFFECTS :: Gastrointestinal - hypermotility, diarrhea Blood - agranulocytosis Blood - thrombocytopenia

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

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 11200 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 :: Intraperitoneal

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 4484 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 - rat

DOSE/DURATION :: 4100 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 :: Intracerebral

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 200 ug/kg

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

TYPE OF TEST :: LD10 - Lethal Dose

ROUTE OF EXPOSURE :: Subcutaneous

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 32 mg/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 :: 20800 ug/kg

TOXIC EFFECTS :: Behavioral - somnolence (general depressed activity) Blood - other changes Nutritional and Gross Metabolic - weight loss or decreased weight gain

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

ROUTE OF EXPOSURE :: Parenteral

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 6 mg/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 :: Unreported

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 29600 ug/kg

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

TYPE OF TEST :: LDLo - Lowest published lethal dose

ROUTE OF EXPOSURE :: Intravenous

SPECIES OBSERVED :: Mammal - dog

DOSE/DURATION :: 3 mg/kg

TOXIC EFFECTS :: Behavioral - somnolence (general depressed activity) Gastrointestinal - hypermotility, diarrhea Blood - normocytic anemia

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 14 mg/kg/7D-I

TOXIC EFFECTS :: Endocrine - changes in spleen weight Immunological Including Allergic - decrease in humoral immune response Nutritional and Gross Metabolic - weight loss or decreased weight gain

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Human - woman

DOSE/DURATION :: 80 ug/kg/D-C

TOXIC EFFECTS :: Tumorigenic - Carcinogenic by RTECS criteria Blood - other changes Blood - lymphoma, including Hodgkin's disease

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Human - man

DOSE/DURATION :: 57 ug/kg/D-C

TOXIC EFFECTS :: Tumorigenic - Carcinogenic by RTECS criteria Blood - other changes Blood - lymphoma, including Hodgkin's disease

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Unreported

SPECIES OBSERVED :: Human - woman

DOSE/DURATION :: 26 mg/kg/2Y-C

TOXIC EFFECTS :: Tumorigenic - Carcinogenic by RTECS criteria Blood - tumors

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Intraperitoneal

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 70 mg/kg/26W-I

TOXIC EFFECTS :: Tumorigenic - neoplastic by RTECS criteria Tumorigenic - tumors at site of application

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Administration onto the skin

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 58 mg/kg/9W-I

TOXIC EFFECTS :: Tumorigenic - equivocal tumorigenic agent by RTECS criteria Lungs, Thorax, or Respiration - tumors Skin and Appendages - tumors

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Intraperitoneal

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 60 mg/kg/26W-I

TOXIC EFFECTS :: Tumorigenic - Carcinogenic by RTECS criteria Lungs, Thorax, or Respiration - tumors Blood - lymphoma, including Hodgkin's disease

TYPE OF TEST :: TD - Toxic dose (other than lowest)

ROUTE OF EXPOSURE :: Intraperitoneal

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 15 mg/kg/6W-I

TOXIC EFFECTS :: Tumorigenic - neoplastic by RTECS criteria Skin and Appendages - tumors

TYPE OF TEST :: TD - Toxic dose (other than lowest)

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Human - man

DOSE/DURATION :: 66 mg/kg/4Y-I

TOXIC EFFECTS :: Tumorigenic - Carcinogenic by RTECS criteria Blood - leukemia

TYPE OF TEST :: TD - Toxic dose (other than lowest)

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Human - man

DOSE/DURATION :: 34 mg/kg/2Y-I

TOXIC EFFECTS :: Tumorigenic - Carcinogenic by RTECS criteria Blood - leukemia

TYPE OF TEST :: TD - Toxic dose (other than lowest)

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Human - woman

DOSE/DURATION :: 12 mg/kg/3Y-I

TOXIC EFFECTS :: Tumorigenic - Carcinogenic by RTECS criteria Blood - leukemia

TYPE OF TEST :: TD - Toxic dose (other than lowest)

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Human - woman

DOSE/DURATION :: 23 mg/kg/2Y-I

TOXIC EFFECTS :: Tumorigenic - Carcinogenic by RTECS criteria Blood - leukemia

TYPE OF TEST :: TD - Toxic dose (other than lowest)

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Human - man

DOSE/DURATION :: 17 mg/kg/4Y-I

TOXIC EFFECTS :: Tumorigenic - Carcinogenic by RTECS criteria Blood - leukemia

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

DOSE :: 3750 ug/kg

SEX/DURATION :: female 25 day(s) pre-mating

TOXIC EFFECTS :: Reproductive - Maternal Effects - menstrual cycle changes or disorders

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Unreported

DOSE :: 8800 ug/kg

SEX/DURATION :: female 1 day(s) pre-mating

TOXIC EFFECTS :: Reproductive - Maternal Effects - ovaries, fallopian tubes Reproductive - Maternal Effects - other effects

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Unreported

DOSE :: 5946 ug/kg

SEX/DURATION :: female 1 day(s) pre-mating

TOXIC EFFECTS :: Reproductive - Maternal Effects - menstrual cycle changes or disorders

TYPE OF TEST :: Specific locus test

TYPE OF TEST :: Specific locus test

TYPE OF TEST :: Sex chromosome loss and nondisjunction

TYPE OF TEST :: Micronucleus test

TYPE OF TEST :: Specific locus test

TYPE OF TEST :: DNA damage

TYPE OF TEST :: Unscheduled DNA synthesis

TYPE OF TEST :: DNA inhibition

TYPE OF TEST :: Sister chromatid exchange

TYPE OF TEST :: Dominant lethal test

TYPE OF TEST :: Heritable translocation test

MUTATION DATA

TYPE OF TEST :: DNA damage

TEST SYSTEM :: Mammal - species unspecified Lymphocyte

DOSE/DURATION :: 2500 nmol/L

REFERENCE :: MUREAV Mutation Research. (Elsevier Science Pub. B.V., POB 211, 1000 AE Amsterdam, Netherlands) V.1- 1964- Volume(issue)/page/year: 368,235,1996 *** REVIEWS *** IARC Cancer Review:Human Sufficient Evidence IMSUDL IARC Monographs, Supplement. (WHO Publications Centre USA, 49 Sheridan Ave., Albany, NY 12210) No.1- 1979- Volume(issue)/page/year: 7,239,1987 IARC Cancer Review:Animal Sufficient Evidence IMEMDT IARC Monographs on the Evaluation of Carcinogenic Risk of Chemicals to Man. (WHO Publications Centre USA, 49 Sheridan Ave., Albany, NY 12210) V.1- 1972- Volume(issue)/page/year: 9,167,1975 IARC Cancer Review:Group 1 IMSUDL IARC Monographs, Supplement. (WHO Publications Centre USA, 49 Sheridan Ave., Albany, NY 12210) No.1- 1979- Volume(issue)/page/year: 7,239,1987 *** NIOSH STANDARDS DEVELOPMENT AND SURVEILLANCE DATA *** NIOSH OCCUPATIONAL EXPOSURE SURVEY DATA : NOES - National Occupational Exposure Survey (1983) NOES Hazard Code - X4742 No. of Facilities: 140 (estimated) No. of Industries: 1 No. of Occupations: 4 No. of Employees: 2418 (estimated) No. of Female Employees: 974 (estimated)

(+-)-A-甲基-4-羧基苯糖胶安全信息

[ 符号 ]:

GHS06, GHS08

[ 信号词 ]:
Danger

[ 危害声明 ]:
H300-H310-H330-H350-H361

[ 警示性声明 ]:
P201-P260-P264-P280-P284-P302 + P350

[ 个人防护装备 ]:
Eyeshields;Faceshields;Gloves;type P2 (EN 143) respirator cartridges

[ 危害码 (欧洲) ]:
T+:Verytoxic;

[ 风险声明 (欧洲) ]:
R45;R46;R26/27/28;R63

[ 安全声明 (欧洲) ]:
S53-S22-S36/37/39-S45

[ 危险品运输编码 ]:
UN 2811 6.1/PG 2

[ WGK德国 ]:
3

[ RTECS号 ]:
AY3675000

[ 包装等级 ]:
II

[ 危险类别 ]:
6.1(a)

[ 海关编码 ]:
2922499990

(+-)-A-甲基-4-羧基苯糖胶合成路线

详细合成路线

(+-)-A-甲基-4-羧基苯糖胶上下游产品

(+-)-A-甲基-4-羧基苯糖胶上游产品

(+-)-A-甲基-4-羧基苯糖胶下游产品

(+-)-A-甲基-4-羧基苯糖胶制备

以对硝基溴苄为原料制得。

(+-)-A-甲基-4-羧基苯糖胶海关

[ 海关编码 ]: 2922499990

[ 中文概述 ]:
2922499990 其他氨基酸及其酯及它们的盐（含有一种以上含氧基的除外）. 增值税率:17.0% 退税率:9.0% 监管条件:AB(入境货物通关单,出境货物通关单) 最惠国关税:6.5% 普通关税:30.0%

[ 申报要素 ]: 品名, 成分含量, 用途, 乙醇胺及其盐应报明色度, 乙醇胺及其盐应报明包装

[ 监管条件 ]: A.入境货物通关单 B.出境货物通关单

[ 检验检疫 ]: P.进境动植物、动植物产品检疫 Q.出境动植物、动植物产品检疫 R.进口食品卫生监督检验 S.出口食品卫生监督检验 M.进口商品检验 N.出口商品检验

[ Summary ]:
HS:2922499990 other amino-acids, other than those containing more than one kind of oxygen function, and their esters; salts thereof VAT:17.0% Tax rebate rate:9.0% Supervision conditions:AB(certificate of inspection for goods inward,certificate of inspection for goods outward) MFN tariff:6.5% General tariff:30.0%

(+-)-A-甲基-4-羧基苯糖胶文献

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