TM-N1324 is an agonist of G protein-coupled receptor 39 (GPR39).1 It is selective for GPR39 over a panel of 165 GPCRs, including the growth hormone (GH) secretagogue receptor (GHS-R) and motilin receptor, at 1 ?M. TM-N1324 induces inositol phosphate accumulation in HEK293 cells expressing human GPR39 (EC50s = 2 and 201 nM in the presence and absence of zinc, respectively) and cAMP accumulation in COS-7 cells expressing human GPR39 (EC50 = 17 nM in the presence of zinc). It decreases ghrelin secretion and increases somatostatin secretion in isolated mouse gastric mucosa cells when used at a concentration of 1 ?M. TM-N1324 (30 mg/kg) decreases food intake during the dark period and body weight in a mouse model of high-fat diet-induced obesity.2
1.Frimurer, T.M., Mende, F., Graae, A.-S., et al.Model-based discovery of synthetic agonists for the Zn2+-sensing G-protein-coupled receptor 39 (GPR39) reveals novel biological functionsJ. Med. Chem.60(3)886-898(2017) 2.Grunddal, K.V., Diep, T.A., Petersen, N., et al.Selective release of gastrointestinal hormones induced by an orally active GPR39 agonistMol. Metab.49101207(2021)