3ws8

Crystal structure of PDE10A in complex with a benzimidazole inhibitor

spinqualitylabelsall models 3ws8, resolution 2.60Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 3ws8 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: MG, X4C, ZN Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function PDE10_HUMAN Plays a role in signal transduction by regulating the intracellular concentration of cyclic nucleotides. Can hydrolyze both cAMP and cGMP, but has higher affinity for cAMP and is more efficient with cAMP as substrate. Publication Abstract from PubMed In this study, we report the identification of potent benzimidazoles as PDE10A inhibitors. We first identified imidazopyridine 1 as a high-throughput screening hit compound from an in-house library. Next, optimization of the imidazopyridine moiety to improve inhibitory activity gave imidazopyridinone 10b. Following further structure-activity relationship development by reducing lipophilicity and introducing substituents, we acquired 35, which exhibited both improved metabolic stability and reduced CYP3A4 time-dependent inhibition. Novel benzimidazole derivatives as phosphodiesterase 10A (PDE10A) inhibitors with improved metabolic stability.,Chino A, Masuda N, Amano Y, Honbou K, Mihara T, Yamazaki M, Tomishima M Bioorg Med Chem. 2014 Jul 1;22(13):3515-26. doi: 10.1016/j.bmc.2014.04.023. Epub , 2014 Apr 20. PMID:24837154 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Phosphodiesterase 3D structures

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