6A3N

Crystal structure of the PDE9 catalytic domain in complex with inhibitor 2

Summary for 6A3N

• Entry DOI: 10.2210/pdb6a3n/pdb
• Descriptor: High affinity cGMP-specific 3',5'-cyclic phosphodiesterase 9A, ZINC ION, MAGNESIUM ION, ... (5 entities in total)
• Functional Keywords: pde9 inhibitor complex, hydrolase
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 2
• Total formula weight: 77080.37

Authors

Wu, Y.N.,Zhou, Q.,Chen, Y.P.,Luo, H.B. (deposition date: 2018-06-15, release date: 2019-04-10, Last modification date: 2024-10-16)

Primary citation

Wu, Y.,Zhou, Q.,Zhang, T.,Li, Z.,Chen, Y.P.,Zhang, P.,Yu, Y.F.,Geng, H.,Tian, Y.J.,Zhang, C.,Wang, Y.,Chen, J.W.,Chen, Y.,Luo, H.B.
Discovery of Potent, Selective, and Orally Bioavailable Inhibitors against Phosphodiesterase-9, a Novel Target for the Treatment of Vascular Dementia.
J. Med. Chem., 62:4218-4224, 2019

PubMed Abstract: To identify phosphodiesterase-9 (PDE9) as a novel target for the treatment of vascular dementia (VaD), a series of pyrazolopyrimidinone analogues were discovered based on a hit 1. Hit-to-lead optimization resulted in a potent inhibitor 2 with excellent selectivity and physicochemical properties to enable in vivo studies. Oral administration of 2 (5.0 mg/kg) caused notable therapeutic effects in the VaD mouse model, providing a promising lead or chemical probe for investigating the biological functions of PDE9 inhibition.

PubMed: 30916555
DOI: 10.1021/acs.jmedchem.8b01041

Experimental method

X-RAY DIFFRACTION (2.6 Å)