中文名称:

FRAX486

中文同义词:

FRAX486是GROUP I PAKS有效抑制剂

英文名称:

Pyrido[2,3-d]pyriMidin-7(8H)-one, 6-(2,4-dichlorophenyl)-8-ethyl-2-[[3-fluoro-4-(1-piperazinyl)phenyl]aMino]-

英文同义词:

FRAX486;6-(2,4-Dichlorophenyl)-8-ethyl-2-[[3-fluoro-4-(1-piperazinyl)phenyl]amino]pyrido[2,3-d]pyrimidin-7(8H)-one;CS-1943;Pyrido[2,3-d]pyriMidin-7(8H)-one, 6-(2,4-dichlorophenyl)-8-ethyl-2-[[3-fluoro-4-(1-piperazinyl)phenyl]aMino]-;6-(2,4-dichlorophenyl)-8-ethyl-2-{[3-fluoro-4-(1-piperazinyl)phen Yl]amino}pyrido[2,3-d]pyrimidin-7(8h)-one FRAX597;6-(2,4-dichlorophenyl)-8-ethyl-2-((3-fluoro-4-(piperazin-1-yl)phenyl)amino)pyrido[2,3-d]pyrimidin-7(8H)-one;FRAX 486; FRAX-486

CAS号:

1232030-35-1

分子式:

C25H23Cl2FN6O

分子量:

513.39

EINECS号:

相关类别:

细胞生物学试剂;抑制剂

Mol文件:

1232030-35-1.mol

储存条件 

-20°C

形态

powder

颜色

white to beige

生物活性

FRAX486 是一种 PAK抑制剂，对 PAK1，PAK2 和 PAK3 的 IC50 值分别为 14，33 和 39 nM。

靶点

PAK1 14 nM (IC 50 ) PAK2 33 nM (IC 50 ) PAK3 39 nM (IC 50 )

PAK1 14 nM (IC 50 )

PAK2 33 nM (IC 50 )

体外研究

In vitro kinase assays using pure enzymes reveal IC 50 s for FRAX486 between 10-100 nM for PAK1-3, while the IC 50 of 779 nM for PAK4 is just below the micromolar range. For FRAX486, an EC 50 value of 500 nM has been reported from cells (5-50 fold higher than IC 50 ). FRAX486 (30 μM) inhibits endothelin-1 and -2 induced contractions. In WPMY-1 cells, FRAX486 (24 h) induces concentration-dependent (1-10 μM) degeneration of actin filaments. This is paralleled by attenuation of proliferation rate, being observed from 1 to 10 μM FRAX486. Cytotoxicity of FRAX486 in WPMY-1 cells is time- and concentration-dependent. FRAX486 significantly reduces the relative proliferation rate in the remaining populations of WPMY-1 cells. While 68% of solvent-treated (24 h) cells shows proliferation, proliferation rate after application of FRAX486 (1-10 μM, 24 h) ranges around 45%. FRAX486 (1-10 μM, 24 h) causes concentration-dependent degeneration of actin filaments. Actin filaments in solvent-treated control cells are arranged to bundles, forming long and thin protrusions, with elongations from adjacent cells overlapping each other. FRAX486 in concentrations of 1 μM causes partial loss of actin organization, including regressing degree of actin polymerization and degeneration of protrusions. FRAX486 in concentrations of 5 or 10 μM causes complete breakdown of filament organization, resulting in a rounded cell shape without protrusions.

体内研究

FRAX486 displays the highest penetrance of blood–brain barrier in DISC1-knockdown C57BL/6 mice. Daily administration of FRAX486, but not that of vehicle, between P35 and P60 blocks the exacerbated spine loss during adolescence. In addition to the significant blockade of spine elimination, a trend of enhanced spine generation is observed by treatment with FRAX486. FRAX486 treatment ameliorates a deficit in prepulse inhibition in adulthood.