5xuj | pdb_00005xuj

Crystal structure of PDE10A in complex with 7-(4-chlorophenyl)-2-methylpyrazolo[1,5-a]pyrimidine

spinqualitylabelsall models 5xuj, resolution 2.44Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 5xuj is a 2 chain structure. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: 8G6, MG, 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 pyrimidoindazoles as phosphodiesterase10A (PDE10A) inhibitors by using the method of fragment-based drug discovery (FBDD). The pyrazolopyridine derivative 2 was found to be a fragment hit compound which could occupy a part of the binding site of PDE10A enzyme by using the method of the X-ray co-crystal structure analysis. On the basis of the crystal structure of compound 2 and PDE10A protein, a number of compounds were synthesized and evaluated, by means of structure-activity relationship (SAR) studies, which culminated in the discovery of a novel pyrimidoindazole derivative 13 having good physicochemical properties. Fragment-Based Discovery of Pyrimido[1,2-b]indazole PDE10A Inhibitors.,Chino A, Seo R, Amano Y, Namatame I, Hamaguchi W, Honbou K, Mihara T, Yamazaki M, Tomishima M, Masuda N Chem Pharm Bull (Tokyo). 2018;66(3):286-294. doi: 10.1248/cpb.c17-00836. PMID:29491261 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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