FRAX486 is a selective inhibitor of group I PAKs with IC50s of 8.25/39.5, /55.3 nM for PAK1/PAK2/PAK3 respectivelt and less potent for PAK4 (IC50=779 nM).
FRAX486 is a p21-activated kinase (PAK) inhibitor with IC50s of 14, 33 and 39 nM for PAK1, PAK2 and PAK3, respectively. in vitro kinase assays using pure enzymes reveal IC50s for FRAX486 between 10-100 nM for PAK1-3, while the IC50 of 779 nM for PAK4 is just below the micromolar range. In WPMY-1 cells, FRAX486 (24 h) induces concentration-dependent (1-10 μM) degeneration of actin filaments. 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[1].
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[2].
体外研究
FRAX486 is a p21-activated kinase (PAK) inhibitor with IC50s of 14, 33 and 39 nM for PAK1, PAK2 and PAK3, respectively. in vitro kinase assays using pure enzymes reveal IC50s for FRAX486 between 10-100 nM for PAK1-3, while the IC50 of 779 nM for PAK4 is just below the micromolar range. In WPMY-1 cells, FRAX486 (24 h) induces concentration-dependent (1-10 μM) degeneration of actin filaments. 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[1].
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