In vitro activity: BI 409306 (SUB 166499) is a novel potent, selective and oral phosphodiesterase 9A (PDE9A) inhibitor. Cyclic guanosine monophosphate (cGMP)-specific phosphodiesterase (PDE) inhibitors are hypothesized to improve cognition in schizophrenia and Alzheimer disease by increasing cGMP levels in certain brain regions. BI 409306 has an IC50 of 52 nM and shows weak activity against other PDEs, such as PDE1A (IC50, 1.4 μM), PDE1C (IC50, 1.0 μM), PDE2A, PDE3A, PDE4B, PDE5A, PDE6AB, PDE7A, and PDE10A (IC50 all> 10 μM); BI-409306 can be used in the research of memory enhancement in CNS disorders. BI 409306 was generally safe and well tolerated, with rapid absorption and elimination. Systemic exposure was higher in CYP2C19 PMs than EMs at the same dose level.

Kinase Assay: BI 409306 (SUB 166499) is a novel potent, selective and oral phosphodiesterase 9A (PDE9A) inhibitor. Cyclic guanosine monophosphate (cGMP)-specific phosphodiesterase (PDE) inhibitors are hypothesized to improve cognition in schizophrenia and Alzheimer disease by increasing cGMP levels in certain brain regions. BI 409306 has an IC50 of 52 nM and shows weak activity against other PDEs, such as PDE1A (IC50, 1.4 μM), PDE1C (IC50, 1.0 μM), PDE2A, PDE3A, PDE4B, PDE5A, PDE6AB, PDE7A, and PDE10A (IC50 all> 10 μM).

Cell Assay: