1,2:5,6-二脱水半乳糖醇

中文名称:

1,2:5,6-二脱水半乳糖醇

中文同义词:

卫矛醇二环氧化物;1,2:5,6-二脱水半乳糖醇

英文名称:

Dianhydrogalactitol

英文同义词:

Dianhydrogalactitol;Dianhydrodulcitolum;1,2,5,6-DIANHYDRODULCITOL;1,2:5,6-Diepoxyhexane-3,4-diol;1,2-Di(oxiranyl)ethylene glycol;Dulcitol diepoxide;NSC-132313;1,2:5,6-Dianhydrogalactitol

CAS号:

23261-20-3

分子式:

C6H10O4

分子量:

146.14

EINECS号:

相关类别:

细胞周期;标准品;中药对照品;APIS

Mol文件:

23261-20-3.mol

熔点 

96.5-98.5 °C

沸点 

185.74°C (rough estimate)

密度 

1.567

折射率 

1.4310 (estimate)

酸度系数(pKa)

13.53±0.20(Predicted)

生物活性

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。

靶点

DNA Alkylator

体外研究

VAL-083 is an alkylating agent that creates N7 methylation on DNA. VAL-083 suppresses U251 and SF188 cell growth and induces apoptosis after 72 h. VAL-083 (5 μM) inhibits the growth of SF188 by ∼95%. VAL-083 inhibits T98G cells growth in a dose-dependent manner (IC 50 <5 μM). VAL-083 (Dianhydrogalactitol) inhibits the proliferation of HUVEC and U251 cells at doses of more than 12.5 μg/mL. VAL-083 (3.125, 6.25, 12.5 μg/mL) also suppresses the migration and invasion, and reduces MMP2, VEGF, VEGFR2, and FGF2 expression in HUVEC and U251 cells. VAL-083 (1,2:5,6-dianhydrogalactitol, 1, 2, 5 μM) dose-dependently induces cell cycle arrest at G2/M phase in the 3 glioma cell lines. VAL-083 activates two parallel signaling cascades, the p53-p21 and the CDC25C-CDK1 cascade. In addition, VAL-083 significantly enhances the radiosensitivity of LN229 cells.

体内研究

VAL-083 (Dianhydrogalactitol; 25, 50, 100 μg/mL) dose-dependently inhibits angiogenesis in zebrafish model. VAL-083 considerably reduces VEGF, VEGFR2, and FGF2 expression at 25 μg/mL, and further causes reduction in FGFR2 expression at 50 μg/mL. VAL-083 (1,2:5,6-dianhydrogalactitol; 5 mg/kg, iv, twice per week for 6 weeks) significantly blocks the growth of LN229 cells in mice with the relative tumor growth rate (T/C) of 22.38%, and the tumor growth inhibitory rate (TGI) of 83.58%. Moreover, VAL-083 dramatically activates the CDC25C-CDK1 cascade in the xenografted tumor moedl.