25 November 2025
Phosphodiesterase-9 (PDE9) is an enzyme that selectively hydrolyzes cyclic guanosine monophosphate (cGMP) with the highest affinity among all phosphodiesterases. By regulating intracellular cGMP levels, PDE9 plays a critical role in neuronal signaling, vascular function, and cell survival. Inhibiting PDE9 prevents the breakdown of cGMP, thereby maintaining its intracellular levels, which potentially improves NMDA receptor signaling and synaptic plasticity. The temporal and spatial expression of PDE9 in various tissues and cell types implies potential roles in pathology, such as central nervous system and cardiovascular diseases. These are not yet fully understood at molecular and cellular levels and further research is warranted.
Our PDE9 inhibitor, BI 409306 (osoresonontrine), is a highly potent and selective molecule with excellent brain penetrance and oral bioavailability. It is well-suited for exploring the role of PDE9 in various indications. To support further advancements in PDE9 research, we offer BI 409306 and its inactive analog BI-8777 free of charge, with full ownership of your results. We encourage you to publish your findings and contribute to the growing understanding of PDE9 inhibition.
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About BI 409306:
BI 409306 (osoresonontrine) is a potent and selective PDE9 inhibitor with double-digit nanomolar in vitro activity on PDE9. BI 409306 exhibits good solubility, excellent fraction unbound, low efflux ratio and high oral availability.
BI 409306 has demonstrated its ability to enhance synaptic plasticity through long-term potentiation (LTP) in rat hippocampal brain slices, supporting its potential to improve memory-related processes. In vivo, BI 409306 showed dose-dependent increases in cGMP levels in the prefrontal cortex and cerebrospinal fluid (CSF), indicating indirect target engagement. The compound improved cognitive performance and memory function in mice via T-maze and novel object recognition tests, and mitigated schizophrenia-related deficits in a maternal immune activation (MIA) mouse model. Additionally, adolescent treatment with BI 409306 prevented adult social interaction deficits in the MIA model.
About opnMe:
opnMe.com, the open innovation portal of Boehringer Ingelheim, fosters science and collaboration initiatives in areas of high unmet medical need. As part of our “Molecules to Order” pillar, we share well-characterized tool compounds free of charge with no IP strings attached. With our “opn2EXPERTS” program and current “techMATCH” call on harnessing intracellular mechanisms, we enlist scientific advice on key biologic issues to fuel further drug discovery and deliver novel solutions that benefit unmet patient needs. Our opn2TALENTS PostDoc grants, provide an opportunity for high-caliber talents to pitch their scientific approaches for well-defined research questions to conduct their research at one of our discovery research sites.