<生产厂家价格>

盐酸依立替康

盐酸依立替康用途

Irinotecan hydrochloride是一种水溶性的拓扑异构酶I抑制剂,主要用于治疗结肠癌和直肠癌。

盐酸依立替康名称

[ CAS 号 ]:
100286-90-6

[ 中文名 ]:
盐酸伊立替康

[ 英文名 ]:
Irinotecan hydrochloride

[中文别名 ]:

[英文别名 ]:

Campto hydrochloride
Campto
Camptothecin 11 hydrochloride
Irinotecan hydrochloride
CPT-11 hydrochloride
Topotecin
irinotecan hydrochloride (anhydrous)
Irinotecan Hcl
CPT 11
Camptothecin analog

盐酸依立替康生物活性

[ 描述 ]:

Irinotecan hydrochloride是一种水溶性的拓扑异构酶I抑制剂,主要用于治疗结肠癌和直肠癌。

[ 相关类别 ]:

信号通路 >> 自噬 >> 自噬

信号通路 >> 细胞周期/DNA损伤 >> 拓扑异构酶

研究领域 >> 癌症

[ 靶点 ]

Topoisomerase I

[体外研究]

伊立替康盐酸盐是拓扑异构酶I抑制剂。伊立替康抑制LoVo和HT-29细胞的生长,IC50分别为15.8±5.1和5.17±1.4μM,并且在LoVo和HT-29细胞中诱导相似量的可切割复合物[2]。伊立替康抑制人脐静脉内皮细胞(HUVEC)的增殖,IC50为1.3μM[3]。

[体内研究]

伊立替康(CPT-11,5mg/kg)在大鼠中连续两周每天通过肿瘤内注射显着抑制肿瘤的生长,并且这种效果也通过渗透微型泵连续腹膜内输注进入小鼠而发生。然而,伊立替康(10 mg/kg)对ip的生长没有影响[1]。伊立替康(CPT-11,100-300mg/kg,ip)显然在第21天抑制无胸腺雌性小鼠中HT-29异种移植物的肿瘤生长。两组伊立替康(125mg/kg)加TSP-1(10mg)/kg /天或伊立替康(150 mg/kg)联合使用TSP-1(每天20 mg/kg)几乎同样有效,分别抑制肿瘤生长84％和89％,两者均比单独使用伊立替康更有效剂量为250和300毫克/千克[3]。

[细胞实验]

将指数生长的细胞接种在20cm 2培养皿中，每个细胞系具有最佳细胞数（对于LoVo细胞为20,000，对于HT-29细胞为100,000）。 2天后，用增加浓度的伊立替康或SN-38处理它们一个细胞倍增时间（LoVo细胞24小时，HT-29细胞40小时）。用0.15M NaCl洗涤后，细胞在正常培养基中进一步生长两次，用胰蛋白酶-EDTA从支持物上分离，并在血细胞计数器中计数。然后将IC50值估计为与不用药物孵育的细胞相比，负责50％生长抑制的药物浓度[2]。

[动物实验]

伊立替康通过瘤内注射0.1cc体积的适当溶液给药，连续两周每天5mg / kg，连续两周，然后休息7天，称为一个治疗周期。大鼠在8周的时间内接受三个周期。对照动物通过瘤内注射以与第II组动物相同的给药规则接受0.1cc无菌0.9％氯化钠溶液[1]。

[参考文献]

[1]. Morales C, et al. Antitumoral effect of irinotecan (CPT-11) on an experimental model of malignant neuroectodermal tumor. J Neurooncol. 2002 Feb;56(3):219-26.

[2]. Pavillard V, et al. Determinants of the cytotoxicity of irinotecan in two human colorectal tumor cell lines. Cancer Chemother Pharmacol. 2002 Apr;49(4):329-35. Epub 2002 Jan 30.

[3]. Allegrini G, et al. Thrombospondin-1 plus irinotecan: a novel antiangiogenic-chemotherapeutic combination that inhibits the growth of advanced human colon tumor xenografts in mice. Cancer Chemother Pharmacol. 2004 Mar;53(3):261-6. Epub 2003 Dec 5.

[相关活性小分子]

盐酸依立替康物理化学性质

[ 沸点 ]:
257 °C

[ 熔点 ]:
250-256°C (dec.)

[ 分子式 ]:
C₃₃H₃₉ClN₄O₆

[ 分子量 ]:
623.139

[ 闪点 ]:
482ºC

[ 精确质量 ]:
622.255798

[ PSA ]:
114.20000

[ LogP ]:
4.76890

[ 外观性状 ]:
黄色结晶粉末

[ 蒸汽压 ]:
1.31E-32mmHg at 25°C

[ 折射率 ]:
67.7 ° (C=1, H2O)

[ 储存条件 ]:
Refrigerator

盐酸依立替康MSDS

详细MSDS(安全技术说明书)

盐酸依立替康毒性和生态

CHEMICAL IDENTIFICATION

RTECS NUMBER :: DW1061000

CAS REGISTRY NUMBER :: 100286-90-6

LAST UPDATED :: 199806

DATA ITEMS CITED :: 20

MOLECULAR FORMULA :: C33-H38-N4-O6.Cl-H

MOLECULAR WEIGHT :: 623.21

HEALTH HAZARD DATA

ACUTE TOXICITY DATA

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

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 867 mg/kg

TOXIC EFFECTS :: Sense Organs and Special Senses (Eye) - effect, not otherwise specified Behavioral - convulsions or effect on seizure threshold Lungs, Thorax, or Respiration - other changes

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

ROUTE OF EXPOSURE :: Intravenous

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 83600 ug/kg

TOXIC EFFECTS :: Tumorigenic - active as anti-cancer agent

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

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 765 mg/kg

TOXIC EFFECTS :: Tumorigenic - active as anti-cancer agent

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

ROUTE OF EXPOSURE :: Intraperitoneal

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 177 mg/kg

TOXIC EFFECTS :: Tumorigenic - active as anti-cancer agent

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

ROUTE OF EXPOSURE :: Intravenous

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 132 mg/kg

TOXIC EFFECTS :: Sense Organs and Special Senses (Eye) - effect, not otherwise specified Behavioral - convulsions or effect on seizure threshold Lungs, Thorax, or Respiration - other changes

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

ROUTE OF EXPOSURE :: Intravenous

SPECIES OBSERVED :: Mammal - dog

DOSE/DURATION :: 40 mg/kg

TOXIC EFFECTS :: Behavioral - convulsions or effect on seizure threshold Gastrointestinal - hypermotility, diarrhea Gastrointestinal - nausea or vomiting

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Intravenous

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 728 mg/kg/26W-C

TOXIC EFFECTS :: Endocrine - other changes Blood - changes in serum composition (e.g. TP, bilirubin, cholesterol) Blood - changes in other cell count (unspecified)

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Intravenous

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 112 mg/kg/4W-I

TOXIC EFFECTS :: Endocrine - changes in thymus weight Blood - pigmented or nucleated red blood cells Blood - other changes

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Intraperitoneal

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 700 mg/kg/14D-I

TOXIC EFFECTS :: Gastrointestinal - ulceration or bleeding from small intestine Gastrointestinal - hypermotility, diarrhea Gastrointestinal - other changes

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Intravenous

SPECIES OBSERVED :: Mammal - dog

DOSE/DURATION :: 44800 ug/kg/28D-C

TOXIC EFFECTS :: Endocrine - changes in spleen weight Blood - changes in serum composition (e.g. TP, bilirubin, cholesterol) Blood - changes in other cell count (unspecified)

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Intravenous

DOSE :: 66 mg/kg

SEX/DURATION :: female 7-17 day(s) after conception

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

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Intravenous

DOSE :: 66 mg/kg

SEX/DURATION :: female 7-17 day(s) after conception

TOXIC EFFECTS :: Reproductive - Specific Developmental Abnormalities - Central Nervous System Reproductive - Specific Developmental Abnormalities - eye/ear Reproductive - Specific Developmental Abnormalities - craniofacial (including nose and tongue)

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Intravenous

DOSE :: 66 mg/kg

SEX/DURATION :: female 7-17 day(s) after conception

TOXIC EFFECTS :: Reproductive - Specific Developmental Abnormalities - skin and skin appendages Reproductive - Specific Developmental Abnormalities - musculoskeletal system Reproductive - Specific Developmental Abnormalities - cardiovascular (circulatory) system

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Intravenous

DOSE :: 66 mg/kg

SEX/DURATION :: female 7-17 day(s) after conception

TOXIC EFFECTS :: Reproductive - Effects on Newborn - live birth index (measured after birth) Reproductive - Effects on Newborn - viability index (e.g., # alive at day 4 per # born alive) Reproductive - Effects on Newborn - growth statistics (e.g.%, reduced weight gain)

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Intravenous

DOSE :: 78 mg/kg

SEX/DURATION :: female 6-18 day(s) after conception

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

DOSE :: 78 mg/kg

SEX/DURATION :: female 6-18 day(s) after conception

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

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Intravenous

DOSE :: 78 mg/kg

SEX/DURATION :: female 6-18 day(s) after conception

TOXIC EFFECTS :: Reproductive - Effects on Embryo or Fetus - fetal death Reproductive - Specific Developmental Abnormalities - craniofacial (including nose and tongue) Reproductive - Specific Developmental Abnormalities - musculoskeletal system

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Intravenous

DOSE :: 78 mg/kg

SEX/DURATION :: female 6-18 day(s) after conception

TOXIC EFFECTS :: Reproductive - Specific Developmental Abnormalities - cardiovascular (circulatory) system

MUTATION DATA

TYPE OF TEST :: DNA inhibition

TEST SYSTEM :: Rodent - mouse Leukocyte

DOSE/DURATION :: 100 umol/L

REFERENCE :: CNREA8 Cancer Research. (Public Ledger Building, Suit 816, 6th & Chestnut Sts., Philadelphia, PA 19106) V.1- 1941- Volume(issue)/page/year: 51,4187,1991

盐酸依立替康安全信息

[ 符号 ]:

GHS07

[ 信号词 ]:
Warning

[ 危害声明 ]:
H302

[ 个人防护装备 ]:
dust mask type N95 (US);Eyeshields;Gloves

[ 危害码 (欧洲) ]:
Xn

[ 风险声明 (欧洲) ]:
R22

[ 危险品运输编码 ]:
NONH for all modes of transport

[ RTECS号 ]:
DW1060750

盐酸依立替康合成路线

详细合成路线

盐酸依立替康上下游产品

盐酸依立替康上游产品

盐酸依立替康下游产品

盐酸依立替康制备

1. 7-乙基喜树碱的制备

在反应瓶中加入喜树碱(camptothecin)1.00g(2.9mmol)、含FeSO4·7H2O 0.30g(1.1mmol)和丙醛2ml的100ml水混合液,于冰浴冷却下滴入浓H2SO4 1ml(搅拌下).再在搅拌下加入30%H2O2 0.72ml(6.4mmol).加毕,于室温下再搅拌反应3h.加水100ml稀释,用氯仿(100ml×3)提取.有机层用无水MgSO4干燥,过滤,滤液浓缩,剩余物用硅胶柱色谱纯化,用2%甲醇/氯仿洗脱.目的组分流出液经后处理,得淡黄色针状结晶7-乙基喜树碱0.84g,mp258~261ºC,收率77%.

2. 7-乙基喜树碱-1-氧的制备

在反应瓶中加入7-乙基喜树碱3.00g(7.97mmol)、乙酸800ml和30%H2O2 50ml,搅拌加热至70~80ºC,在该温度下搅拌反应3.5h.于45~55ºC将反应液浓缩至原体积的1/3,剩余物倒入冰水3000ml中,析出沉淀,过滤,滤饼经重结晶纯化后,得橙黄色针状结晶7-乙基喜树碱-1-氧2.4g,mp255ºC,收率78%.

3. 7-乙基-10-羟基喜树碱的制备

在反应瓶中加入7-乙基喜树碱-1-氧1.00g(2.6mmol)和1mol/LH2SO4 2.6ml溶于二氧六环1000ml的溶液,用N2鼓泡换气20min.在搅拌下#用带有硅硼玻璃(Pyrex,派瑞克斯)滤片的高压汞灯(450W,Usio,UM-452)照射30min.将反应液浓缩至干,剩余物用10%甲醇/氯仿50ml溶解.用水500ml洗涤,有机层和无机层都通过一装有硅藻土的柱子,二相中的不溶物均被吸附其上,然后用10%甲醇/氯仿(200ml×3)洗脱.洗脱液浓缩后,剩余物用甲醇洗后重结晶,得淡黄色针状结晶7-乙基-10-羟基喜树碱0.5g,收率49%,mp216ºC.

4. 7-乙基-10-氯甲酰氧基喜树碱的制备

在反应瓶中加入7-乙基-10-羟基喜树碱5.00g(12.8mmol)、二氧六环(干燥的)4000ml和三乙胺50ml,于室温,搅拌下通入光气(由3.75ml双光气作用于活性炭所产生),用TLC跟踪,确认原料消耗尽,定反应终点.继续搅拌反应1h. 过滤,滤液减压浓缩至干.剩余物用丙酮浸渍后过滤,抽干,得无色粉状物5.2g,收率90%.

5. 伊立替康的制备

在反应瓶中加入7-乙基-10-氯甲酰氧基喜树碱3.0g(6.6mmol0、二氯甲烷50ml和甲醇150ml、吡啶15ml,搅拌溶解,于室温搅拌下滴加4-哌啶基哌啶3.3g(19.6mmol)的二氯甲烷溶液.加毕,在室温下继续搅拌反应15h.减压浓缩至干,剩余物溶于二氯甲烷,用NaHCO3溶液洗涤,无水MgSO4干燥.过滤,滤液减压浓缩,剩余物经硅胶柱色谱纯化,4%甲醇/二氯甲烷洗脱. 得淡黄色粉状物伊立替康3.09g,收率79.8%,mp222~223ºC.

6. 盐酸伊立替康的合成

在反应瓶中加入伊立替康2g(3.4mmol),加乙醇适量后,搅拌微加热溶解,控制20ºC通HCl气体至溶液呈酸性(pH4), 减压浓缩至干,剩余用水重结晶得盐酸伊立替康1.5g,mp256.5ºC,收率65.2%.

盐酸依立替康文献

Aqueous-core PEG-coated PLA nanocapsules for an efficient entrapment of water soluble anticancer drugs and a smart therapeutic response.

Eur. J. Pharm. Biopharm. 89 , 30-9, (2015)

Novel PEGylated PLA nanocapsules (PEG-AcPLA nanocapsules), loading high percentage of water soluble drugs have been formulated by using multiple emulsion technique without using conventional stabilize...

Assessment of the efficacy of anticancer drugs by amino acid metabolomics using fluorescence derivatization-HPLC.

Anal. Sci. 30(7) , 751-8, (2014)

Metabolomic studies conducted for evaluating cancer pathogenesis and progression by monitoring the amino acids metabolic balance hold great promise for assessing current and future anticancer treatmen...

Evaluation of the in vitro/in vivo potential of five berries (bilberry, blueberry, cranberry, elderberry, and raspberry ketones) commonly used as herbal supplements to inhibit uridine diphospho-glucuronosyltransferase.

Food Chem. Toxicol. 72 , 13-9, (2014)

In this study, we evaluated inhibitory potentials of popularly-consumed berries (bilberry, blueberry, cranberry, elderberry, and raspberry ketones) as herbal supplements on UGT1A1, UGT1A4, UGT1A6, UGT...

更多文献