放线菌酮_MSDS_作用_用途_放线菌酮CAS号【66-81-9】

Cycloheximide (Naramycin A) 是真核生物蛋白质合成的抑制剂,抑制体内蛋白质合成和RNA合成的 IC50 值分别为532.5 nM 和 2880 nM。

是一种在真核生物中对蛋白质生物合成过程有抑制效应的化合物，它是灰色链霉菌（Streptomyces griseus）的一种产物。它通过干扰蛋白质合成过程中的易位步骤而阻碍翻译过程。在生物药学研究中放线菌酮常被用来抑制生物体外真核细胞的蛋白质合成。这个方法非常有效、快速和廉价。而且通过将放线菌酮从试管中去除掉可以很快地取消它的作用。
由于放线菌酮拥有非常强烈的毒性，包括损害DNA、导致畸形胎儿和其它对繁殖过程的效应（包括出生障碍和对精子的毒性），它一般只被用在体外的研究应用中，它不适宜在人体内作为抗菌素使用。过去在农业中它被用来作为杀真菌剂，但是由于对它的危险性的认识不断提高这个用法已经很少了。
碱可以破坏放线菌酮，因此假如工作台面或者容器被放线菌酮污染后只要使用无害的碱溶液（比如肥皂）洗就可以了。

[ 描述 ]:

Cycloheximide (Naramycin A) 是真核生物蛋白质合成的抑制剂,抑制体内蛋白质合成和RNA合成的 IC50 值分别为532.5 nM 和 2880 nM。

[ 相关类别 ]:

信号通路 >> 自噬 >> 自噬

信号通路 >> 细胞周期/DNA损伤 >> DNA/RNA合成

信号通路 >> 抗感染 >> 真菌

研究领域 >> 感染

天然产物 >> 其他

[ 靶点 ]

IC50: 532.5 nM (protein synthesis), 2.88 μM (RNA synthesis)[1]

[体外研究]

环己酰亚胺(CHX)是用于抑制蛋白质合成的最常用的实验室试剂。已显示环己酰亚胺阻断真核翻译的延伸期。环己酰亚胺结合核糖体并抑制eEF2介导的易位。令人惊讶的是,环己酰亚胺允许在停止任何进一步延伸之前进行一个完整的易位循环。推测环己酰亚胺环己酰亚胺需要E位点结合的脱酰基tRNA用于活性[1]。

[体内研究]

在用200μA休克训练之前,小鼠接受30,60或120mg/kg的环己酰亚胺注射。环己酰亚胺对记忆试验试验的潜伏期有显着影响(P <0.001)。在盐水对照组中,这种休克水平导致测试试验的潜伏期明显高于训练时的潜伏期。所测试的最低剂量的环己酰亚胺(30mg/kg)的注射导致试验试验的潜伏期显着高于盐水对照组中观察到的潜伏期。接受两种较高剂量的环己酰亚胺中的任一种的小鼠在试验试验中具有与盐水组相当的潜伏期,即,在这些条件下较高剂量既不增强也不损害记忆,导致倒U型剂量-反应曲线。用于环己酰亚胺增强记忆[2]。通过氯化三苯基氯化物(TTC)的梗塞面积的形态测量分析测量的梗塞体积分别在HI后0或6小时给予环己酰亚胺时显着降低92％和61％,但如果环己酰亚胺显示梗塞减少的显着趋势与HI对照组相比,在缺氧缺血(HI)后12小时施用,并且当施用延迟至HI后24小时时未观察到保护作用[3]。

[细胞实验]

为了测试细胞增殖，将每孔3000-5000个细胞（HeLa，HTB1和HEK 293T细胞; Jurkat，BT 474，HCC 1395，HCC 1937，HCC 2218和MDA MB231细胞; MCF 10A）接种在96孔板中并且允许坚持过夜。然后加入以指定浓度（0.1nM-1000μM）溶解在DMSO中的环己酰亚胺，将细胞再温育24小时。以每孔1μCi加入[3H] - 胸苷，并继续孵育另外7小时。用PBS洗涤细胞两次，然后用胰蛋白酶消化，然后用Tomtec收集器收集细胞并结合GF / C过滤垫。然后通过闪烁计数测量胸苷摄取[1]。

[动物实验]

小鼠[2]在该实验中使用雄性ICR小鼠（大约2个月大）。环己酰亚胺以0（盐水对照），30,60或120mg / kg的浓度IP施用。在训练前30分钟施用环己酰亚胺注射。 120mg / kg剂量通常用于研究小鼠的健忘症。注意，在大鼠（1-3mg / kg）中遗忘的环己酰亚胺剂量比在小鼠中低得多，这与大鼠和小鼠的LD50s的类似差异一致。注射后30-60分钟测量的环己酰亚胺剂量为120-150mg / kg导致脑蛋白质合成的约95％抑制; 30mg / kg的剂量产生约80％的脑蛋白质合成抑制。大鼠[3]在甲氧氟烷麻醉下，在7日龄Sprague Dawley大鼠幼仔中进行单侧颈动脉结扎。颈部在中线切开，右颈总动脉用4-0丝永久结扎。每只动物的手术总时间从未超过5分钟。手术后，将大鼠返回母亲进行恢复并喂食2小时。然后将幼崽置于100分钟的缺氧期（8％O2,92％N2）中，将它们置于部分浸没在温控水浴中的气密室中，以使室内的环境温度保持恒定36°。 C。在HI与环己酰亚胺治疗组中，大鼠幼仔在恢复0,6,12或24小时时以0.6mg / kg的剂量腹膜内注射环己酰亚胺，并向HI对照给予等体积的生理盐水。组。然后，将大鼠幼崽送回大坝直至牺牲;在HI后48和72小时分别在深度戊巴比妥麻醉（60mg / kg，腹膜内）下进行流式细胞术和氯化三苯基四氮唑（TTC）获得全脑组织。

[参考文献]

[1]. Schneider-Poetsch T, et al. Inhibition of eukaryotic translation elongation by cycloheximide and lactimidomycin. Nat Chem Biol. 2010 Mar;6(3):209-217.

[2]. Gold PE, et al. Cycloheximide impairs and enhances memory depending on dose and footshock intensity. Behav Brain Res. 2012 Aug 1;233(2):293-7.

[3]. Park W S, et al. Therapeutic window for cycloheximide treatment after hypoxic-ischemic brain injury in neonatal rats. J Korean Med Sci. 2006 Jun;21(3):490-4.

[相关活性小分子]

[ 密度 ]:
1.1±0.1 g/cm3

[ 沸点 ]:
491.8±10.0 °C at 760 mmHg

[ 熔点 ]:
111-116 °C

[ 分子式 ]:
C₁₅H₂₃NO₄

[ 分子量 ]:
281.347

[ 闪点 ]:
251.2±19.0 °C

[ 精确质量 ]:
281.162720

[ PSA ]:
83.47000

[ LogP ]:
0.56

[ 外观性状 ]:
灰白色至淡黄褐色的粉末

[ 蒸汽压 ]:
0.0±2.8 mmHg at 25°C

[ 折射率 ]:
1.499

[ 储存条件 ]:
库房通风低温干燥,与食品原料分开储运

[ 水溶解性 ]:
2.1 g/100 mL (2 ºC)

详细MSDS(安全技术说明书)

CHEMICAL IDENTIFICATION

RTECS NUMBER :: MA4375000

CHEMICAL NAME :: Glutarimide, 3-(2-(3,5-dimethyl-2-oxocyclohexyl)-2-hydroxyethyl)-

CAS REGISTRY NUMBER :: 66-81-9

BEILSTEIN REFERENCE NO. :: 0088868

LAST UPDATED :: 199709

DATA ITEMS CITED :: 85

MOLECULAR FORMULA :: C15-H23-N-O4

MOLECULAR WEIGHT :: 281.39

WISWESSER LINE NOTATION :: T6VMVTJ E1YQ- BL6VTJ D1 F1

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 :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 2 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 :: Intraperitoneal

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 3700 ug/kg

TOXIC EFFECTS :: Behavioral - somnolence (general depressed activity) Gastrointestinal - hypermotility, diarrhea Skin and Appendages - hair

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

ROUTE OF EXPOSURE :: Subcutaneous

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 2500 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 :: 2 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 - rat

DOSE/DURATION :: 133 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 :: Oral

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 133 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 :: Intraperitoneal

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 100 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 :: Subcutaneous

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 160 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 :: 150 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 :: Oral

SPECIES OBSERVED :: Mammal - dog

DOSE/DURATION :: 65 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 :: Mammal - dog

DOSE/DURATION :: 1 mg/kg

TOXIC EFFECTS :: Gastrointestinal - nausea or vomiting

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

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Primate - monkey

DOSE/DURATION :: 60 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 :: Intraperitoneal

SPECIES OBSERVED :: Mammal - cat

DOSE/DURATION :: 4 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 - rabbit

DOSE/DURATION :: 17 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 :: Oral

SPECIES OBSERVED :: Rodent - guinea pig

DOSE/DURATION :: 65 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 :: Intraperitoneal

SPECIES OBSERVED :: Rodent - guinea pig

DOSE/DURATION :: 60 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 :: Subcutaneous

SPECIES OBSERVED :: Rodent - guinea pig

DOSE/DURATION :: 60 mg/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 :: Intraperitoneal

SPECIES OBSERVED :: Rodent - hamster

DOSE/DURATION :: 40 mg/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 :: Subcutaneous

SPECIES OBSERVED :: Bird - chicken

DOSE/DURATION :: 2 mg/kg

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

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Intraperitoneal

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 400 mg/kg/4W-I

TOXIC EFFECTS :: Liver - changes in liver weight Endocrine - changes in thymus weight Immunological Including Allergic - decrease in humoral immune response

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Primate - monkey

DOSE/DURATION :: 56 mg/kg/7D-I

TOXIC EFFECTS :: Liver - other changes Kidney, Ureter, Bladder - other changes Blood - changes in erythrocyte (RBC) count

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Intraperitoneal

DOSE :: 1 mg/kg

SEX/DURATION :: female 4 day(s) after conception

TOXIC EFFECTS :: Reproductive - Maternal Effects - uterus, cervix, vagina

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Intraperitoneal

DOSE :: 300 ug/kg

SEX/DURATION :: female 13 day(s) after conception

TOXIC EFFECTS :: Reproductive - Fertility - post-implantation mortality (e.g. dead and/or resorbed implants per total number of implants) Reproductive - Effects on Embryo or Fetus - fetotoxicity (except death, e.g., stunted fetus)

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Intraperitoneal

DOSE :: 250 ug/kg

SEX/DURATION :: female 10 day(s) after conception

TOXIC EFFECTS :: Reproductive - Specific Developmental Abnormalities - Central Nervous System Reproductive - Specific Developmental Abnormalities - craniofacial (including nose and tongue) Reproductive - Specific Developmental Abnormalities - cardiovascular (circulatory) system

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Intraperitoneal

DOSE :: 1 mg/kg

SEX/DURATION :: female 15 day(s) after conception

TOXIC EFFECTS :: Reproductive - Effects on Embryo or Fetus - fetotoxicity (except death, e.g., stunted fetus) Reproductive - Specific Developmental Abnormalities - hepatobiliary system

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Intraperitoneal

DOSE :: 1 mg/kg

SEX/DURATION :: female 18 day(s) after conception

TOXIC EFFECTS :: Reproductive - Specific Developmental Abnormalities - Central Nervous System Reproductive - Effects on Newborn - growth statistics (e.g.%, reduced weight gain)

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Parenteral

DOSE :: 750 ug/kg

SEX/DURATION :: female 18 day(s) after conception

TOXIC EFFECTS :: Reproductive - Effects on Embryo or Fetus - extra-embryonic structures (e.g., placenta, umbilical cord) Reproductive - Effects on Embryo or Fetus - fetotoxicity (except death, e.g., stunted fetus)

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Intraperitoneal

DOSE :: 30 mg/kg

SEX/DURATION :: female 10 day(s) after conception

TOXIC EFFECTS :: Reproductive - Specific Developmental Abnormalities - musculoskeletal system

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Intraperitoneal

DOSE :: 30 mg/kg

SEX/DURATION :: female 9 day(s) after conception

TOXIC EFFECTS :: Reproductive - Fertility - post-implantation mortality (e.g. dead and/or resorbed implants per total number of implants) Reproductive - Effects on Embryo or Fetus - fetotoxicity (except death, e.g., stunted fetus) Reproductive - Effects on Embryo or Fetus - fetal death

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Subcutaneous

DOSE :: 80 mg/kg

SEX/DURATION :: female 11 day(s) after conception

TOXIC EFFECTS :: Reproductive - Effects on Embryo or Fetus - fetal death

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Subcutaneous

DOSE :: 5 mg/kg

SEX/DURATION :: female 11 day(s) after conception

TOXIC EFFECTS :: Reproductive - Fertility - post-implantation mortality (e.g. dead and/or resorbed implants per total number of implants)

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Intraperitoneal

DOSE :: 5 mg/kg

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

TOXIC EFFECTS :: Reproductive - Fertility - other measures of fertility

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Intraperitoneal

DOSE :: 250 ug/kg

SEX/DURATION :: female 10 day(s) after conception

TOXIC EFFECTS :: Reproductive - Specific Developmental Abnormalities - Central Nervous System Reproductive - Specific Developmental Abnormalities - craniofacial (including nose and tongue) Reproductive - Specific Developmental Abnormalities - cardiovascular (circulatory) system

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Parenteral

DOSE :: 5 ug/kg

SEX/DURATION :: female 1 day(s) after conception

TOXIC EFFECTS :: Reproductive - Fertility - other measures of fertility

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Intraperitoneal

DOSE :: 60 mg/kg

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

TOXIC EFFECTS :: Reproductive - Fertility - other measures of fertility

TYPE OF TEST :: Morphological transformation

TYPE OF TEST :: Mutation test systems - not otherwise specified

TYPE OF TEST :: DNA inhibition

TYPE OF TEST :: Mutation test systems - not otherwise specified

TYPE OF TEST :: Cytogenetic analysis

TYPE OF TEST :: Micronucleus test

TYPE OF TEST :: Micronucleus test

TYPE OF TEST :: DNA inhibition

TYPE OF TEST :: Mutation test systems - not otherwise specified

TYPE OF TEST :: Cytogenetic analysis

MUTATION DATA

TYPE OF TEST :: Mutation test systems - not otherwise specified

TEST SYSTEM :: Mammal - pig Kidney

DOSE/DURATION :: 1 mg/L

REFERENCE :: CYGEDX Cytology and Genetics (English Translation). Translation of TGANAK. (Allerton Press Inc., 150 Fifth Ave., New York, NY 10011) V.8- 1974- Volume(issue)/page/year: 12(1),1,1978 *** REVIEWS *** TOXICOLOGY REVIEW CRTXB2 CRC Critical Reviews in Toxicology. (CRC Press, Inc., 2000 Corporate Blvd., NW, Boca Raton, FL 33431) V.1- 1971- Volume(issue)/page/year: 2,159,1973 *** U.S. STANDARDS AND REGULATIONS *** EPA FIFRA 1988 PESTICIDE SUBJECT TO REGISTRATION OR RE-REGISTRATION FEREAC Federal Register. (U.S. Government Printing Office, Supt. of Documents, Washington, DC 20402) V.1- 1936- Volume(issue)/page/year: 54,7740,1989 *** NIOSH STANDARDS DEVELOPMENT AND SURVEILLANCE DATA *** NIOSH OCCUPATIONAL EXPOSURE SURVEY DATA : NOHS - National Occupational Hazard Survey (1974) NOHS Hazard Code - 84338 No. of Facilities: 968 (estimated) No. of Industries: 3 No. of Occupations: 6 No. of Employees: 4439 (estimated) NOES - National Occupational Exposure Survey (1983) NOES Hazard Code - 84338 No. of Facilities: 234 (estimated) No. of Industries: 2 No. of Occupations: 7 No. of Employees: 3059 (estimated) No. of Female Employees: 2370 (estimated)

[ 符号 ]:

GHS06, GHS08, GHS09

[ 信号词 ]:
Danger

[ 危害声明 ]:
H300-H341-H360D-H411

[ 警示性声明 ]:
Missing Phrase - N15.00950417-P201-P280-P308 + P313

[ 个人防护装备 ]:
Eyeshields;Faceshields;full-face respirator (US);Gloves;multi-purpose combination respirator cartridge (US);type ABEK (EN14387) respirator filter

[ 危害码 (欧洲) ]:
T+:Verytoxic;N:Dangerous for the environment;

[ 风险声明 (欧洲) ]:
R28;R51/53;R61;R68

[ 安全声明 (欧洲) ]:
S53-S45-S61

[ 危险品运输编码 ]:
UN 2811 6.1/PG 1

[ WGK德国 ]:
3

[ RTECS号 ]:
MA4375000

[ 包装等级 ]:
II

[ 危险类别 ]:
6.1(a)

[ 海关编码 ]:
29419000

详细合成路线

放线菌酮上游产品

放线菌酮下游产品

[ 海关编码 ]: 29419000

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