FRAX1036 inhibition of group I p21-activated kinase (PAK) isoforms. (A) Chemical structure of the group I PAK inhibitor, FRAX1036. (B) Concentration-response analysis of FRAX1036 against PAK1, PAK2 or PAK4. Concentration response curves were generated in duplicate and represent one of at least three experiments for PAK1 and PAK2 with similar results. Data shown for PAK4 represent one of two experiments with similar results. Each curve is normalized to zero and 100% based on no enzyme or DMSO, respectively. (C) Pharmacodynamic changes induced by FRAX1036 dose–response. MDA-MB175 cells were treated with increasing concentrations of FRAX1036 for 24 hours. Cell lysates were immunoblotted with antibodies against biomarkers involved in PAK1 effector and survival signaling.