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Computer-Aided Selective Optimization of Side Activities of Talinolol

 
: 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.

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ACS medicinal chemistry letters 10 (2019), No.6, pp.899-903
ISSN: 1948-5875 (online)
English
Journal Article
Fraunhofer IME ()

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 in vivo activity in a rat model of diabetic neuropatic pain.

: http://publica.fraunhofer.de/documents/N-558506.html