BLU0588 is a selective PRKACA inhibitor. BLU0588 inhibits PRKACA catalytic activity with a half-maximal inhibitory concentration (IC50) of 1 nM.

PRKACA:4 nM (Kd), RKACA (PHOS cellsphorylation of VASP Ser157 in Huh7 cells):25.0 nM, PRKACA:1 nM

RKACA cellular IC50 values were 25.0 nM with BLU0588, which were determined from inhibition of VASP Ser157 phosphorylation in forskolin-stimulated Huh7 cells[1].

For in vivo studies, mice were given either BLU0588 at 30 mg/kg and 75 mg/kg once daily (QD) and monitored for 24 hours. Plasma concentrations peaked within 2–4 hours of QD dosing. For BLU0588-treated mice, phosphorylated VASP was reduced to 19% and 4% of baseline phosphorylation levels with 30 mg/kg QD and 75 mg/kg QD, respectively, 4 hours after dosing; phosphorylated VASP levels fully recovered by 24 hours post administration of 30 mg/kg QD. When mice harboring FLC PDX tumors were treated with BLU0588 given orally at 30 mg/kg QD, by Day 34 tumor growth was inhibited by 48.5% (P = 0.003)[1].