TABLE 1

Selectivity profile of BAY 73-6691 against different human PDE isoenzymes All enzymes were human recombinant, except for PDE5, which was purified from human platelets. IC50 values were determined from sigmoidal curves by plotting the percentage of PDE activity versus the log compound concentration. IC50 is defined as the concentration of the inhibitor (in nanomoles) required to reduce the cyclic nucleotide hydrolyzing activity of tested PDEs by 50%. The relative selectivity for PDE9A was determined by calculating the ratio between the IC50 for each PDE and the IC50 for PDE9.

IC50 Ratio
nM
PDE9A 55 ± 9
PDE1C 1400 ± 350 25
PDE2A ≫4000 ≫73
PDE3B ≫4000 ≫73
PDE4B ≫4000 ≫73
PDE5A ≫4000 ≫73
PDE7B ≫4000 ≫73
PDE8A ≫4000 ≫73
PDE10A ≫4000 ≫73
PDE11A 2600 ± 400 47