23261-20-3

• 常用中文名：1,2:5,6-二脱水半乳糖醇
• 常用英文名：VAL-083
• CAS号：23261-20-3
• 分子式：C₆H₁₀O₄
• 分子量：146.14100
• 相关类别： 信号通路 细胞周期/DNA损伤 DNA烷基化剂/交联剂
• 发布时间：2018-08-17 00:03:27
• 更新时间：2024-01-05 18:05:59
• 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。

名称

• 中文名: 1,2:5,6-二脱水半乳糖醇
• 英文名: 1,2-bis(oxiran-2-yl)ethane-1,2-diol
• 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

物化性质

• 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℃

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.

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

安全

• 海关编码: 2910900090

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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%