3WS9

Crystal structure of PDE10A in complex with a benzimdazole inhibitor

Summary for 3WS9

• Entry DOI: 10.2210/pdb3ws9/pdb
• Related: 3WS8
• 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: 80099.13

Authors

Amano, Y.,Honbou, K. (deposition date: 2014-03-04, release date: 2014-06-04, Last modification date: 2024-05-29)

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

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

Experimental method

X-RAY DIFFRACTION (2.99 Å)