6HGX

Soluble epoxide hydrolase in complex with 1-(4-((4-(tert-butyl)morpholin-2-yl)methoxy)phenyl)-3-cyclohexylurea

Summary for 6HGX

• Entry DOI: 10.2210/pdb6hgx/pdb
• Related: 6HGV
• Descriptor: Bifunctional epoxide hydrolase 2, MAGNESIUM ION, 1-[4-[[(2~{S})-4-~{tert}-butylmorpholin-2-yl]methoxy]phenyl]-3-cyclohexyl-urea, ... (4 entities in total)
• Functional Keywords: inhibitor, complex, seh, hydrolase
• Biological source: Homo sapiens
• Total number of polymer chains: 1
• Total formula weight: 40062.37

Authors

Kramer, J.S.,Pogoryelov, D.,Hiesinger, K.,Proschak, E. (deposition date: 2018-08-23, release date: 2019-07-03, Last modification date: 2024-01-17)

Primary citation

Hiesinger, K.,Kramer, J.S.,Achenbach, J.,Moser, D.,Weber, J.,Wittmann, S.K.,Morisseau, C.,Angioni, C.,Geisslinger, G.,Kahnt, A.S.,Kaiser, A.,Proschak, A.,Steinhilber, D.,Pogoryelov, D.,Wagner, K.,Hammock, B.D.,Proschak, E.
Computer-Aided Selective Optimization of Side Activities of Talinolol.
Acs Med.Chem.Lett., 10:899-903, 2019

PubMed Abstract: 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 activity in a rat model of diabetic neuropatic pain.

PubMed: 31223445
DOI: 10.1021/acsmedchemlett.9b00075

Experimental method

X-RAY DIFFRACTION (2.16 Å)