ISDA: 3WI2

Deposition Date 2013-09-04

Release Date 2013-12-11

Last Version Date 2024-05-29

Entry Detail

PDB ID:

3WI2

Keywords:

HYDROLASE/HYDROLASE INHIBITOR

Title:

Crystal structure of PDE10A in complex with inhibitor

Biological Source:

Source Organism(s):

Homo sapiens (Taxon ID: 9606)

Expression System(s):

Escherichia coli

Method Details:

Experimental Method:

X-RAY DIFFRACTION

Resolution:

2.26 Å

R-Value Free:

0.32

R-Value Work:

0.25

R-Value Observed:

0.25

Space Group:

P 21 21 21

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Macromolecular Entities

Structures with similar UniProt ID

Protein Blast

Polymer Type:polypeptide(L)
Molecule:cAMP and cAMP-inhibited cGMP
Gene (Uniprot):PDE10A
Chain IDs:A, B
Chain Length:345
Number of Molecules:2
Biological Source:Homo sapiens

UniProt ID:Q9Y233 Pfam ID:PF00233 EC:3.1.4.17

Ligand Molecules

P98

Primary Citation

Design and synthesis of novel benzimidazole derivatives as phosphodiesterase 10A inhibitors with reduced CYP1A2 inhibition.

Hamaguchi, W, Masuda, N, Isomura, M, Miyamoto, S, Kikuchi, S, Amano, Y, Honbou, K, Mihara, T, Watanabe, T.Show

Bioorg Med Chem 21 7612 ? (2013)

PMID: 24238902 DOI: .

Abstact

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.

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Primary Citation of related structures

Abstact

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