Predicted time course and experimentally measured cAMP levels under varying drug combination conditions. Besides modeling results (B, D, E), panel A and C show experimentally measured cAMP levels (marked with black dots). Single and combinatory effect of Cilostamide (drug doses range: 10, 50, 200 μM) and Iloprost (drug doses range: 2, 5, 20 nM) on the cAMP level (A): The resulting cAMP concentrations, depicted as the mean of triplicate measurements (± SEM), successively rise according to the corresponding elevated drug doses and show a clear synergistic effect. 3D-plots show interpolated cAMP levels (z-axis; cAMP surface) of estimated or experimentally measured plateaus of cAMP reached at various synergistically activating or inhibitory drug combinations (x- and y-axes): Combination (B) of Iloprost and Milrinone (AC activation, PDE inhibition); (C) of Iloprost and Cilostamide (AC activation, PDE inhibition); (D) of Forskolin and Milrinone (AC activation, PDE inhibition); (E) of Milrinone together with an unspecified inhibitor of adenylyl cyclase (simultaneous PDE and AC inhibition). Dots mark means of experimentally measured cAMP level plateaus (C) and accordingly predicted cAMP values (B, D, E) reached after the respective chosen concentration and combination of drugs was administered. For further details on drug combination interactions see Additional file 1, Table S8.1.