3WS8

Crystal structure of PDE10A in complex with a benzimidazole inhibitor

Summary for 3WS8

Entry DOI	10.2210/pdb3ws8/pdb
Related	3WS9
Descriptor	cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A, ZINC ION, MAGNESIUM ION, ... (5 entities in total)
Functional Keywords	phosphodiesterase, 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	80127.18
Authors	Amano, Y.,Honbou, K. (deposition date: 2014-03-04, release date: 2014-06-04, Last modification date: 2023-11-08)
Primary citation	Chino, A.,Masuda, N.,Amano, Y.,Honbou, K.,Mihara, T.,Yamazaki, M.,Tomishima, M. Novel benzimidazole derivatives as phosphodiesterase 10A (PDE10A) inhibitors with improved metabolic stability. Bioorg.Med.Chem., 22:3515-3526, 2014 Cited by PubMed Abstract: 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. PubMed: 24837154 DOI: 10.1016/j.bmc.2014.04.023 PDB entries with the same primary citation
Experimental method	X-RAY DIFFRACTION (2.6 Å)

Structure validation