GSK256073

GSK256073 is a potent, selective and orally active GPR109A agonist and a long-lasting and non-flushing HCA2 full agonist with a pEC₅₀ of 7.5 (human HCA2). GSK256073 acutely improves glucose homeostasis via inhibition of lipolysis and has the potential for the study of type 2 diabetes mellitus (T2DM)and dyslipidemia^[1][2]. GPR109A: G-protein coupled receptor 109A; HCA2: hydroxy-carboxylic acid receptor 2 IC50 & Target: IC50: GPR109A (G-protein coupled receptor 109A); HCA2 (hydroxy-carboxylic acid receptor 2)^[1][2] In Vitro: GSK256073 is approximately 10-fold more potent than niacin against human HCA2 (pEC₅₀ value of 7.5 compared to 6.7 for niacin), has good activity versus the rat orthologue of HCA2 (pEC₅₀ value of 6.9 compared to 6.4 for niacin) in membranes prepared from Chinese hamster ovary cellsexpressing recombinant human HCA2^[2].
GSK256073 (100 μM) suppresses cAMP elevation induced by isoprenaline (100 nM) in rat primary adipocytes^[2].
In Vivo: GSK256073 (oral adminstration; 1, 30 and 100 mg/kg; in rat) shows that the fall in NEFA is of rapid onset and that the maximum is dose-related with inhibitions of 74, 81 and 88%, respectively. Triglycerides decrease is followed as a similar pattern,although the duration was longer with a decrease of 91% still present 6 h post dose at 10 mg/kg^[2].
GSK256073 (intravenous injection; 1-10 mg/kg) produces a dose related decrease in NEFA. However, the increase in ear temperature induced by 10 mg/kg i.v. GSK256073 is only 40% of that induced by 10 mg/kg i.v. niacin^[2].