| Title : Computer-Aided Selective Optimization of Side Activities of Talinolol - Hiesinger_2019_ACS.Med.Chem.Lett_10_899 |
| Author(s) : Hiesinger K , Kramer JS , Achenbach J , Moser D , Weber J , Wittmann SK , Morisseau C , Angioni C , Geisslinger G , Kahnt AS , Kaiser A , Proschak A , Steinhilber D , Pogoryelov D , Wagner K , Hammock BD , Proschak E |
| Ref : ACS Med Chem Lett , 10 :899 , 2019 |
|
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. |
| PubMedSearch : Hiesinger_2019_ACS.Med.Chem.Lett_10_899 |
| PubMedID: 31223445 |
| Gene_locus related to this paper: human-EPHX2 |
| Inhibitor | G3W Talinolol Morpholino-Talinolol |
| Gene_locus | human-EPHX2 |
| Family | Epoxide_hydrolase |
| Structure | 6HGX 6HGV 6HGW |
Hiesinger K, Kramer JS, Achenbach J, Moser D, Weber J, Wittmann SK, Morisseau C, Angioni C, Geisslinger G, Kahnt AS, Kaiser A, Proschak A, Steinhilber D, Pogoryelov D, Wagner K, Hammock BD, Proschak E (2019)
Computer-Aided Selective Optimization of Side Activities of Talinolol
ACS Med Chem Lett
10 :899
Hiesinger K, Kramer JS, Achenbach J, Moser D, Weber J, Wittmann SK, Morisseau C, Angioni C, Geisslinger G, Kahnt AS, Kaiser A, Proschak A, Steinhilber D, Pogoryelov D, Wagner K, Hammock BD, Proschak E (2019)
ACS Med Chem Lett
10 :899