6a3n

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

Structural highlights 6a3n is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.6Å Ligands: , , Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function PDE9A_HUMAN Hydrolyzes the second messenger cGMP, which is a key regulator of many important physiological processes. Publication Abstract from PubMed 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. Discovery of Potent, Selective, and Orally Bioavailable Inhibitors against Phosphodiesterase-9, a Novel Target for the Treatment of Vascular Dementia.,Wu Y, Zhou Q, Zhang T, Li Z, Chen YP, Zhang P, Yu YF, Geng H, Tian YJ, Zhang C, Wang Y, Chen JW, Chen Y, Luo HB J Med Chem. 2019 Apr 3. doi: 10.1021/acs.jmedchem.8b01041. PMID:30916555 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Phosphodiesterase 3D structures

spinqualitylabelsall models 6a3n, resolution 2.60Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image