A Matsuo

AR Thomsen

C Southan

DE Gloriam

F Shi

J Duan

J Greenwood

J Wang

JL Sharman

JP Overington

K Liu

LA Hu

MM Mysinger

R Fredriksson

SA Hitchcock

SL Dixon

U Susens

V Isberg

WL Jorgensen

Scientific Reports

AbstractGPR139 is an orphan class A G protein-coupled receptor found mainly in the central nervous system. It has its highest expression levels in the hypothalamus and striatum, regions regulating metabolism and locomotion, respectively, and has therefore been suggested as a potential target for obesity and Parkinson’s disease. The two aromatic amino acids L-Trp and L-Phe have been proposed as putative endogenous agonists, and three structurally related benzohydrazide, glycine benzamide, and benzotriazine surrogate agonist series have been published. Herein, we assayed 158 new analogues selected from a pharmacophore model, and identified 12 new GPR139 agonists, containing previously untested bioisosteres. Furthermore, we present the first combined structure-activity relationships, and a refined pharmacophore model to serve as a rationale for future ligand identification and optimization.</jats:p

Mohamed A. Shehata

Anne C. Nøhr

Delphine Lissa

Christoph Bisig

Vignir Isberg

Kirsten B. Andersen

Kasper Harpsøe

Fredrik Björkling

Hans Bräuner-Osborne

David E. Gloriam

Crossref

Novel Agonist Bioisosteres and Common Structure-Activity Relationships for The Orphan G Protein-Coupled Receptor GPR139

Novel Agonist Bioisosteres and Common Structure-Activity Relationships for The Orphan G Protein-Coupled Receptor GPR139

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