Fig. 1

MHY4571 inhibits PKA activity. A The chemical structure of MHY4571. B Docking simulation of adenosine-triphosphate (ATP) to PKA Cα (PDB code number 4WB5) (left). Simulation of daphnetin to the ATP binding site of PKA Cα (middle). Simulation of MHY4571 to the ATP binding site of PKA Cα (right). Binding affinity to PKA Cα of daphnetin, a known PKA inhibitor and MHY4571 to PKA Cα. C PKA kinase activity assay was performed to confirm PKA kinase activity using total cell lysates treated with MHY4571 at 0, 2.5, 5, 7.5, and 10 μM. Data are the means ± SD (n = 3). Significance was calculated by the student's t-test (*P < 0.05 and **P < 0.01 vs. vehicle-treated cells). D Selectivity and target profile of 7.5 μM MHY4571 against 410 kinases in a multikinase inhibition assay in vitro. Shown are kinases whose activity was inhibited by > 50% at the tested dose