< 生产厂家价格 >

1,2:5,6-二脱水半乳糖醇

1,2:5,6-二脱水半乳糖醇用途

VAL-083 是一种烷化剂 (alkylator),能够在 DNA 上产生 N7 甲基化,具有抗肿瘤活性。

点击显示

1,2:5,6-二脱水半乳糖醇名称

[ CAS 号 ]:
23261-20-3

[ 中文名 ]:
1,2:5,6-二脱水半乳糖醇

[ 英文名 ]:
VAL-083

[英文别名 ]:

Galactitol,1,2:5,6-dianhydro
1,2:5,6-Diepoxydulcitol
Dulcitoldiepoxide
5,6-Diepoxydulcitol
Dianhydrogalactitol
1,2,5,6-dianhydro-galactitol
1,2-5,6-dianhydro-dulcitol
Dianhydrodulcitol
VAL-083

1,2:5,6-二脱水半乳糖醇生物活性

[ 描述 ]:

VAL-083 是一种烷化剂 (alkylator),能够在 DNA 上产生 N7 甲基化,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[1]

[体外研究]

VAL-083是一种烷基化剂,可在DNA上产生N7甲基化。 VAL-083在72小时后抑制U251和SF188细胞生长并诱导细胞凋亡。 VAL-083(5μM)抑制SF188的生长~95％。 VAL-083以剂量依赖性方式抑制T98G细胞生长(IC50 <5μM)[1]。 VAL-083(二脱水半乳糖醇)以超过12.5μg/ mL的剂量抑制HUVEC和U251细胞的增殖。 VAL-083(3.125,6.25,5.5μg/ mL)也抑制迁移和侵袭,并减少HUVEC和U251细胞中MMP2,VEGF,VEGFR2和FGF2的表达[2]。 VAL-083(1,2：5,6-二脱水半乳糖醇,1,2,5μM)剂量依赖性地诱导3种神经胶质瘤细胞系中G2/M期的细胞周期停滞。 VAL-083激活两个平行的信号级联,即p53-p21和CDC25C-CDK1级联。此外,VAL-083显着增强了LN229细胞的放射敏感性[3]。

[体内研究]

VAL-083(二脱水半乳糖醇;25,50,100μg/ mL)剂量依赖性地抑制斑马鱼模型中的血管生成。 VAL-083在25μg/ mL时显着降低VEGF,VEGFR2和FGF2的表达,并进一步导致50μg/ mL时FGFR2表达降低[2]。 VAL-083(1,2：5,6-二脱水半乳糖醇; 5mg/kg,静脉注射,每周两次,共6周)显着阻断小鼠LN229细胞的生长,相对肿瘤生长率(T/C)为22.38 ％,肿瘤生长抑制率(TGI)为83.58％。此外,VAL-083显着激活异种移植肿瘤模型中的CDC25C-CDK1级联[3]。

[细胞实验]

通过CCK8测定法测量VAL-083在HUVEC和U251细胞HUVEC和U251细胞增殖中的作用。将细胞以每孔1×10 4个细胞的命运接种到96孔板中。孵育过夜后，细胞附着，然后加入各种浓度的VAL-083，持续24小时;然后向每个孔中加入10μLCCK8，并在37℃下孵育2小时。光密度在450nm处测量[2]。

[动物实验]

将小鼠[3] LN229细胞悬浮于MEM中，并在6-8周龄时将每只小鼠2×10 6个细胞皮下注射到BALB / c裸鼠的胁腹中。肿瘤体积计算如下：0.5×L×W2。将携带肿瘤的小鼠分成两组（n = 8），具有相似的平均体积（载体：108±4mm 3对比VAL-083：107±4mm 3）。然后，两组均进行以下治疗：VAL-083治疗组以5mg / kg或10μL/ g静脉注射VAL-083，每周两次，持续6周。载体组以10μL/ g静脉注射生理盐水，每周三次，持续6周。肿瘤体积每周测量两次[3]。

[参考文献]

[1]. Kaiji Hu, et al. Abstract 811: VAL083, a novel N7 alkylating agent, surpasses temozolomide activity and inhibits cancer stem cells providing a new potential treatment option for glioblastoma multiforme. Cancer Research. 2012 Mar 31-Apr 4.

[2]. Jiang X, et al. Dianhydrogalactitol, a potential multitarget agent, inhibits glioblastoma migration, invasion, and angiogenesis. Biomed Pharmacother. 2017 Jul;91:1065-1074.

[3]. Peng C, et al. 1,2:5,6-dianhydrogalactitol inhibits human glioma cell growth in vivo and in vitro by arresting the cell cycle at G2/M phase. Acta Pharmacol Sin. 2017 Apr;38(4):561-570.

[相关活性小分子]

1,2:5,6-二脱水半乳糖醇物理化学性质

[ 密度 ]:
1.567

[ 沸点 ]:
348ºC at 760mmHg

[ 分子式 ]:
C₆H₁₀O₄

[ 分子量 ]:
146.14100

[ 闪点 ]:
164.3ºC

[ 精确质量 ]:
146.05800

[ PSA ]:
65.52000

[ 储存条件 ]:
2-8℃

1,2:5,6-二脱水半乳糖醇毒性和生态

CHEMICAL IDENTIFICATION

RTECS NUMBER :: LW5320000

CAS REGISTRY NUMBER :: 23261-20-3

LAST UPDATED :: 199703

DATA ITEMS CITED :: 20

MOLECULAR FORMULA :: C6-H10-O4

MOLECULAR WEIGHT :: 146.16

WISWESSER LINE NOTATION :: T3OTJ BYQYQ- BT3OTJ

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 :: 14 mg/kg

TOXIC EFFECTS :: Gastrointestinal - other changes 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 - rat

DOSE/DURATION :: 11 mg/kg

TOXIC EFFECTS :: Gastrointestinal - other changes Nutritional and Gross Metabolic - weight loss or decreased weight gain

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

ROUTE OF EXPOSURE :: Intravenous

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 16 mg/kg

TOXIC EFFECTS :: Gastrointestinal - other changes Nutritional and Gross Metabolic - weight loss or decreased weight gain

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

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 7899 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 - mouse

DOSE/DURATION :: 15 mg/kg

TOXIC EFFECTS :: Gastrointestinal - other changes Nutritional and Gross Metabolic - weight loss or decreased weight gain

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

ROUTE OF EXPOSURE :: Subcutaneous

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 16500 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 :: 21 mg/kg

TOXIC EFFECTS :: Gastrointestinal - other changes 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 :: 16 mg/kg

TOXIC EFFECTS :: Behavioral - somnolence (general depressed activity) Gastrointestinal - hypermotility, diarrhea Nutritional and Gross Metabolic - weight loss or decreased weight gain

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

ROUTE OF EXPOSURE :: Intravenous

SPECIES OBSERVED :: Rodent - rabbit

DOSE/DURATION :: 14 gm/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 :: Intravenous

SPECIES OBSERVED :: Mammal - dog

DOSE/DURATION :: 20 mg/kg/5D-I

TOXIC EFFECTS :: Blood - agranulocytosis Blood - changes in bone marrow (not otherwise specified) Related to Chronic Data - death

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Intravenous

SPECIES OBSERVED :: Primate - monkey

DOSE/DURATION :: 20 mg/kg/5D-I

TOXIC EFFECTS :: Behavioral - somnolence (general depressed activity) Behavioral - food intake (animal) Nutritional and Gross Metabolic - weight loss or decreased weight gain

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Intravenous

SPECIES OBSERVED :: Rodent - rabbit

DOSE/DURATION :: 87500 ug/kg/70D-I

TOXIC EFFECTS :: Blood - changes in bone marrow (not otherwise specified)

TYPE OF TEST :: DNA adduct

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

TYPE OF TEST :: DNA inhibition

MUTATION DATA

TYPE OF TEST :: DNA inhibition

TEST SYSTEM :: Rodent - rabbit Bone marrow

DOSE/DURATION :: 136 umol/L

REFERENCE :: BCPCA6 Biochemical Pharmacology. (Pergamon Press Inc., Maxwell House, Fairview Park, Elmsford, NY 10523) V.1- 1958- Volume(issue)/page/year: 25,1705,1976

点击显示

1,2:5,6-二脱水半乳糖醇安全信息

[ 海关编码 ]:
2910900090

1,2:5,6-二脱水半乳糖醇上下游产品

1,2:5,6-二脱水半乳糖醇上游产品

1,2:5,6-二脱水半乳糖醇下游产品

1,2:5,6-二脱水半乳糖醇海关

[ 海关编码 ]: 2910900090

[ 中文概述 ]:
2910900090. 三节环环氧化物，环氧醇（酚，醚），包括其卤化，磺化，硝化或亚硝化的衍生物. 增值税率:17.0%. 退税率:13.0%. 监管条件:无. 最惠国关税:5.5%. 普通关税:30.0%

[ 申报要素 ]: 品名, 成分含量, 用途

[ Summary ]:
2910900090. epoxides, epoxyalcohols, epoxyphenols and epoxyethers, with a three-membered ring, and their halogenated, sulphonated, nitrated or nitrosated derivatives. VAT:17.0%. Tax rebate rate:13.0%. . MFN tariff:5.5%. General tariff:30.0%