Table 1.
Inhibitory constant (K i) values for ITI-214 measured against a panel of phosphodiesterase isoforms. Values were determined as described in “Materials and methods” section using bovine or human recombinant enzymes, as indicated. Since for all PDE assays, substrate concentration was below K m for the enzyme data are reported as K i values. K i values for ITI-214 against each PDE isoform were then expressed as a ratio over the K i of the compound for human recombinant PDE1A enzyme
| PDE target | Ki (μM) | Ratio PDEx/PDE1A |
|---|---|---|
| hPDE1A | 0.000034 | 1 |
| hPDE1B | 0.00038 | 11.5 |
| hPDE1C | 0.000037 | 1.1 |
| PDE1 (bovine brain) | 0.000058 | 1.7 |
| hPDE2A | >10 | 29,411 |
| hPDE3B | 3.1 | 93,939 |
| hPDE4D | 0.033 | 970 |
| r-bovine PDE5A | 0.63 | 19,090 |
| bovine retina PDE6 | 0.32 | 9696 |
| hPDE7B | 0.36 | 10,909 |
| hPDE8A | 3 | 90,909 |
| hPDE9A | >10 | 294,117 |
| hPDE10A | 1.8 | 54,545 |
| hPDE11A | 1.3 | 39,393 |
hPDE1A human recombinant PDE1A, hPDE1B human recombinant PDE1B, hPDE1C human recombinant PDE1C, hPDE2A human recombinant PDE2A, hPDE3B human recombinant PDE3B, hPDE4A human recombinant PDE4A, r-bovine PDE5A recombinant bovine PDE5A, hPDE7B human recombinant PDE7B, hPDE8A human recombinant PDE8A, hPDE9A human recombinant PDE9A, hPDE10a human recombinant PDE10A, hPDE11A human recombinant 11A