依托泊苷磷酸酯

中文名称:

依托泊苷磷酸酯

中文同义词:

依托泊甙磷酸酯;依托泊苷磷酸酯(磷酸依托泊甙、磷酸依托泊苷);依托泊苷磷酸酯;磷酸依托泊甙;磷酸依托泊苷

英文名称:

Etoposide phosphate

英文同义词:

ETOPOPHOS;ETOPOSIDE PHOSPHATE;ETOPOSIDE PHOSPHONATE;ETOPOSIDE PHOSPHONATE,　ETOPOPHOS;BMY-40481, Etoposide 4-Dihydrogenphosphate;Etoposide 4-Phosphate;(5R,5aR,8aR,9S)-5-[3,5-DiMethoxy-4-(phosphonooxy)phenyl]-9-[[4,6-O-(1R)-ethylidene-β-D-glucopyranosyl]oxy]-5,8,8a,9-tetrahydrofuro[3,4:6,7]naphtho[2,3-d]-1,3-dioxol-6(5aH)-one;[5R-[5α,5aβ,8aα,9β(R*)]]-5-[3,5-DiMethoxy-4-(phosphonooxy)phenyl]-9-[(4,6-O-ethylidene-β-D-glucopyranosyl)oxy]-5,8,8a,9-tetrahydrofuro[3,4:6,7]naphtho[2,3-d]-1,3-dioxol-6(5aH)-one

CAS号:

117091-64-2

分子式:

C29H33O16P

分子量:

668.54

EINECS号:

630-364-1

相关类别:

信号转导通路激酶抑制剂;Antineoplastic;Carbohydrates Derivatives;Drug Analogues;Heterocycles;Inhibitors;Intermediates Fine Chemicals;Pharmaceuticals;API

Mol文件:

117091-64-2.mol

沸点 

907.7±75.0 °C(Predicted)

密度 

1?+-.0.1 g/cm3(Predicted)

储存条件 

-20°C

酸度系数(pKa)

1.13±0.50(Predicted)

生物活性

Etoposide phosphate (BMY-40481) 是一种有效的抗癌 (anti-cancer) 化疗试剂和一种选择性拓扑异构酶 II (topoisomerase II) 抑制剂，可以防止 DNA 链的重新连接。Etoposide phosphate 是依托泊苷的磷酸酯前药，被认为与 Etoposide 活性相当。Etoposide phosphate 诱导细胞周期阻滞、凋亡 (apoptosis) 和自噬 (autophagy)。

靶点

Topoisomerase II

Topoisomerase II

体外研究

Etoposide phosphate is a water-soluble derivative and probable prodrug of etoposide characterized by the presence of a phosphate group in position 4 of the E ring of the etoposide molecule.Etoposide phosphate (0-1 μM; 72 hours) inhibits HCT116 FBXW +/+ , FBXW -/- and p53 -/- as a dose-dependent manner, exhibits IC 50 values of 0.945 μM; 0.375 μM; and 1.437 μM, respectively.Etoposide phosphate (25 μM; 6 hours) delays p53 recover in FBXW7-deficient cells. In addition, FBXW7 expression is disappeared in FBXW7 -/- cells. Cell Viability Assay Cell Line: FBXW +/+ , FBXW -/- and p53 -/- cell Concentration: 0.025 μM, 0.05 μM, 0.075 μM, 0.1 μM, 0.2 μM, 0.4 μM, 0.6 μM, 0.8 μM, 1 μM Incubation Time: 72 hours Result: Inhibited HCT116 FBXW +/+ , FBXW -/- and p53 -/- cell growth as a concentration manner. Western Blot Analysis Cell Line: HCT116 FBXW7 +/+ or FBXW7 -/- cells Concentration: 25 μM Incubation Time: 6 hours Result: Exhibited that the recovery of p53 levels after DNA damage is mediated by FBXW7.

Cell Line:

FBXW +/+ , FBXW -/- and p53 -/- cell

Concentration:

0.025 μM, 0.05 μM, 0.075 μM, 0.1 μM, 0.2 μM, 0.4 μM, 0.6 μM, 0.8 μM, 1 μM

Incubation Time:

72 hours

Result:

Inhibited HCT116 FBXW +/+ , FBXW -/- and p53 -/- cell growth as a concentration manner.

Cell Line:

HCT116 FBXW7 +/+ or FBXW7 -/- cells

Concentration:

25 μM

Incubation Time:

6 hours

Result:

Exhibited that the recovery of p53 levels after DNA damage is mediated by FBXW7.

体内研究

Etoposide phosphate (intravenous injection; 50, 100, or 150 mg/kg; single dose) has clinical symptomology of progressive ataxia, impaired righting reflex, and splaying and paresis of fore- and hindlimbs at day 8 in female CD-1 mice. Animal Model: Female CD-1 mice Dosage: 50, 100, or 150 mg/kg Administration: Intravenous injection; single dose Result: Observed degeneration of dorsal root ganglion cells and axonal degeneration of their distal and proximal processes in peripheral nerves, dorsal spinal roots, and dorsal funiculi of the spinal cord at all doses under light microscopy (LM).

Animal Model:

Female CD-1 mice

Dosage:

50, 100, or 150 mg/kg

Administration:

Intravenous injection; single dose

Result:

Observed degeneration of dorsal root ganglion cells and axonal degeneration of their distal and proximal processes in peripheral nerves, dorsal spinal roots, and dorsal funiculi of the spinal cord at all doses under light microscopy (LM).