Biocore analysis of cilostazol-PDE3B/Epac-1 interaction.

(A) Cilostazol, cilostamide, and milrinone interfere with association of PDE3B-binding Epac-1 peptides-1 to PDE3B. The above-mentioned compounds’ competition with PDE3B-binding Epac-1 peptides-1 (5 μM) binding to Epac-1-binding PDE3B peptide was evaluated (n = 4; ** p < 0.01 vs. 5 μM PDE3B-binding Epac-1 peptides-1, randomized Dunnett’s test). (B) Cilostazol, cilostamide, and milrinone interfere with association of PDE3B-binding Epac-1 peptides-2 to PDE3B. These compounds’ competition with Epac-1 peptides-2 (5 μM) binding to Epac-1-binding PDE3B peptide was evaluated (n = 4; * p < 0.05, ** p < 0.01 vs. 5 μM PDE3B-binding Epac-1 peptides-2, randomized Dunnett’s test). (C) Direct bindings of cilostazol, cilostamide, and milrinone to PI3Kγ-binding PDE3B peptide. Relative responses of PI3Kγ-binding PDE3B peptide to drugs at concentrations of 0.3125, 0.625, 1.25, 2.5, and 5 μM (n = 4).