FRAX486 is potent, selective, brain-penetrant group I PAKs inhibitor with IC50 of 8.25, 39.5, and 55.3 nM for PAK1, PAK2 and PAK3, respectively.
FRAX486 poorly inhibits group II PAK (PAK4) with IC50 of 779 nM.
FRAX486 rescued increased density of apical dendritic spines, reversed hyperactivity and repetitive behaviors in Fmr1 KO mice.
FRAX486 ameliorateed adolescent synapse loss in the prefrontal cortex and adult behavior change in a DISC1 knockdown mouse model.
FRAX486 combined with midostaurin significantly prolonged leukemia progression-free survival in FLT3 D835H PDX-ALL model.
