5XUI

Crystal structure of PDE10A in complex with 2-methyl-5-[2-([1,2,4]triazolo[1,5-a]pyrimidin-2-yl)et hyl]pyrazolo[1,5-a]pyrimidin-7-ol

Summary for 5XUI

• Entry DOI: 10.2210/pdb5xui/pdb
• Descriptor: cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A, ZINC ION, MAGNESIUM ION, ... (5 entities in total)
• Functional Keywords: pde10a inhibitor, hydrolase, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor
• Biological source: Homo sapiens (Human)
• Cellular location: Cytoplasm: Q9Y233
• Total number of polymer chains: 2
• Total formula weight: 79687.59

Authors

Amano, Y.,Honbou, K. (deposition date: 2017-06-23, release date: 2018-03-14, Last modification date: 2024-11-06)

Primary citation

Chino, A.,Seo, R.,Amano, Y.,Namatame, I.,Hamaguchi, W.,Honbou, K.,Mihara, T.,Yamazaki, M.,Tomishima, M.,Masuda, N.
Fragment-Based Discovery of Pyrimido[1,2-b]indazole PDE10A Inhibitors.
Chem. Pharm. Bull., 66:286-294, 2018

PubMed Abstract: 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.

PubMed: 29491261
DOI: 10.1248/cpb.c17-00836

Experimental method

X-RAY DIFFRACTION (2.77 Å)