中文名称:

1,4-二氨基-2,3-二氰基-1,4-双(邻氨基苯巯基)丁二烯

中文同义词:

1,4-二氨基-2,3-二氰基-1,4-双(邻氨基苯巯基)丁二烯;1,4-二氨基-2,3-二氰基-1,4-双(邻氨基苯硫基)丁二烯;MEK抑制剂(U0126)

英文名称:

U0126

英文同义词:

U0126;1,4-DIAMINO-2,3-DICYANO-1,4-BIS(2-AMINOPHENYLTHIO)BUTADIENE;1,4-DIAMINO-2,3-DICYANO-1,4-BIS(2-AMINOPHYNYLTIO)BUTADIENE;1,4-DIAMINO-2,3-DICYANO-1,4-BIS(O-AMINOPHENYLMERCAPTO)BUTADIENE;1,4-DIAMINO-2,3-DICYANO-1;UO 126;U0126 >99%;2,3-Bis[amino[(2-aminophenyl)thio]methylene]butanedinitrile

CAS号:

109511-58-2

分子式:

C18H16N6S2

分子量:

380.49

EINECS号:

相关类别:

细胞生物学试剂;Signalling;Protein Kinase;Inhibitor

Mol文件:

109511-58-2.mol

熔点 

approximate 154℃(dec.)

沸点 

565.1±50.0 °C(Predicted)

密度 

1.44

RTECS号

EJ9710000

储存条件 

Desiccate at +4°C

形态

White solid

酸度系数(pKa)

2.11±0.10(Predicted)

水溶解性 

Soluble in DMSO. Poorly soluble in ethanol and water

生物活性

U0126 是一种有效，非 ATP 竞争性的，选择性的 MEK1 和 MEK2 抑制剂，IC50 分别为 72 nM 和 58 nM。U0126-EtOH 是一种自噬 (autophagy) 和线粒体自噬 (mitophagy) 抑制剂。

靶点

MEK2 60 nM (IC 50 ) MEK1 70 nM (IC 50 )

MEK2 60 nM (IC 50 )

MEK1 70 nM (IC 50 )

体外研究

Treatment with U0126 efficiently reduces progeny virus titers of all tested strains in A549 cells. While nM concentrations of U0126 are efficient to reduce H1N1v and H5N1 (MB1), μM concentrations of U0126 are required to reduce the virus titer of H5N1 (GSB) and H7N7. The EC 50 values for U0126-EtOH against H1N1v are 1.2±0.4 μM in A549 cells and 74.7±1.0 μM in MDCKII cells. Rat hepatocarcinoma cells (FAO) stimulated by fetal calf serum (FCS) exhibits a significant proportion in S phase (32.62%) whereas U0126 strongly decreases the proportion of cells in S phase (9.92%) and increases the proportion of cells in G 0 -G 1 phase and to a lesser extent in G 2 /M. Cell Viability Assay Cell Line: A549 and MDCK II cells. Concentration: 0.001-1000 μM. Incubation Time: 48 h. Result: The EC 50 values for U0126 against H1N1v were 1.2 ± 0.4 μM in A549 cells and 74.7 ± 1.0 μM in MDCKII cells

Cell Line:

A549 and MDCK II cells.

Concentration:

0.001-1000 μM.

Incubation Time:

48 h.

Result:

The EC 50 values for U0126 against H1N1v were 1.2 ± 0.4 μM in A549 cells and 74.7 ± 1.0 μM in MDCKII cells

体内研究

Mice are treated daily with U0126-EtOH (U0126; i.p., 10.5 mg/kg). In control experiment, tumor sizes are constant or slightly increase all over the kinetic. At the opposite, in all U0126-EtOH experiments, engraftment and early tumor growth are significantly decreased. Furthermore, a 60-70% reduction in the volume of tumors treated with U0126-EtOH is obtained 9 days after injection and thereafter. Rats are subjected to 120 minutes transient middle cerebral artery occlusion (tMCAO) and thereafter treated with the U0126-EtOH (U0126; i.p., 30 mg/kg) at 0 and 24 hours of reperfusion. After treatment with U0126-EtOH, the vasoconstriction to S6c is markedly reduced. Animal Model: Athymic female nude mice (SWISS, nu/nu). Dosage: 10.5 mg/kg. Administration: Intraperitoneal injection daily. Result: Inhibited tumor growth. Animal Model: Twelve-week-old female Wistar rats (250 to 265 g) . Dosage: 30 mg/kg. Administration: Intraperitoneally. Result: The vasoconstriction to S6c is markedly reduced.

Animal Model:

Athymic female nude mice (SWISS, nu/nu).

Dosage:

10.5 mg/kg.

Administration:

Intraperitoneal injection daily.

Result:

Inhibited tumor growth.

Animal Model:

Twelve-week-old female Wistar rats (250 to 265 g) .

Dosage:

30 mg/kg.

Administration:

Intraperitoneally.

Result:

The vasoconstriction to S6c is markedly reduced.