Selective optimization of side activities is a valuable source of novel lead structures in drug discovery. In this study, a computer-aided approach was used to deorphanize the pleiotropic cholesterol-lowering effects of the beta-blocker talinolol, which result from the inhibition of the enzyme soluble epoxide hydrolase (sEH). X-ray structure analysis of the sEH in complex with talinolol enables a straightforward optimization of inhibitory potency. The resulting lead structure exhibited in vivo activity in a rat model of diabetic neuropatic pain.
        
Representative scheme of Epoxide_hydrolase structure and an image from PDBsum server
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PDB-Sum
6HGV Previously Class, Architecture, Topology and Homologous superfamily - PDB-Sum server
FSSP
6HGVFold classification based on Structure-Structure alignment of Proteins - FSSP server