3WI2

Crystal structure of PDE10A in complex with inhibitor

Summary for 3WI2

• Entry DOI: 10.2210/pdb3wi2/pdb
• Descriptor: cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A, ZINC ION, MAGNESIUM ION, ... (5 entities in total)
• Functional Keywords: phosphodiesterase, cgmp binding, 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: 80179.25

Authors

Amano, Y. (deposition date: 2013-09-04, release date: 2013-12-11, Last modification date: 2024-05-29)

Primary citation

Hamaguchi, W.,Masuda, N.,Isomura, M.,Miyamoto, S.,Kikuchi, S.,Amano, Y.,Honbou, K.,Mihara, T.,Watanabe, T.
Design and synthesis of novel benzimidazole derivatives as phosphodiesterase 10A inhibitors with reduced CYP1A2 inhibition.
Bioorg.Med.Chem., 21:7612-7623, 2013

PubMed Abstract: A novel class of phosphodiesterase 10A (PDE10A) inhibitors with reduced CYP1A2 inhibition were designed and synthesized starting from 2-{[(1-phenyl-1H-benzimidazol-6-yl)oxy]methyl}quinoline (1). Introduction of an isopropyl group at the 2-position and a methoxy group at the 5-position of the benzimidazole ring of lead compound 1 resulted in the identification of 2-{[(2-isopropyl-5-methoxy-1-phenyl-1H-benzimidazol-6-yl)oxy]methyl}quinoline (25b), which exhibited potent PDE10A inhibitory activity with reduced CYP1A2 inhibitory activity compared to compound 1.

PubMed: 24238902
DOI: 10.1016/j.bmc.2013.10.035

Experimental method

X-RAY DIFFRACTION (2.26 Å)