Biochem/physiol Actions

FRAX486 is a potent, group I-selective p21-activated kinase (PAK) inhibitor (PAK1/2/3 IC50 = 8.25/39.5/55.3 nM; group II PAK4 IC50 = 779 nM). FRAX486 effectively inhibits PAK-mediated PKD1 Ser203 phosphorylation and PAK1/2 Ser144/141 autophosphorylation upon angiotensin II (ANGII) stimulation of rat IEC-18 cells (IC50 ~0.5 µM) and exhibits in vivo efficacy in rescuing the autism-like phenotypes among Fmr1 knockout fragile syndrome (FXS) mice (20 mg/kg s.c.) as well as in ameliorating schizophrenia-associated dendritic spine deterioration among Disc1 knockdown mice (10 µg/g or 10 mg/kg i.p.) with good pharmacokinetic properties and blood–brain barrier (BBB) permeability.