Key result
Recent PDE1 inhibitors lack high selectivity over other PDEs, risking severe clinical side effects.
Why the study?
PDE1 is a potential target for diseases like cardiovascular disease, and numerous structurally diverse inhibitors have been patented, warranting an overview of recent patent literature.
The development of highly selective PDE1 inhibitors remains a top priority to minimize side effects and explore clinical indications beyond CNS diseases.
May warrant caution advancing non-selective PDE1 inhibitors; leaves open priority for selective agents to expand indications.
INTRODUCTION: PDE1 has been demonstrated to be a potential drug target for a variety of diseases, such as Alzheimer's disease and cardiovascular disease. In the past decades, numerous PDE1 inhibitors with structural diversities have been developed and patented by pharmaceutical companies, providing drug candidates for exploring novel disease indications of PDE1. AREA COVERED: This review aims to provide an overview of PDE1 inhibitors reported in patents from 2008 to present. EXPERT OPINION: Among current PDE1 inhibitors, only a few of them showed high selectivity over other PDEs, which might cause severe side effects in the clinic. The development of highly selective PDE1 inhibitors is still the 'top priority' in the following research. The selective recognition mechanism of PDE1 with inhibitors should be further elucidated by X-ray crystallography in order to provide evidence for the rational design of selective PDE1 inhibitors. In addition, PDE1 inhibitors should be applied to different clinical indications beyond CNS diseases.
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Le et al. (2022) conducted a review in Alzheimer's disease and cardiovascular disease. PDE1 inhibitors was evaluated. PDE1 inhibitors developed in recent patents (2008-present) largely lack high selectivity over other PDEs, which may lead to severe clinical side effects.
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