GSK256073 (C09-1134-703)

GSK256073 is a potent, selective and orally active GPR109A agonist and a long-lasting and non-flushing HCA2 full agonist with a pEC 50 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 GPR109A: G-protein coupled receptor 109A; HCA2: hydroxy-carboxylic acid receptor 2In VitroGSK256073 is approximately 10-fold more potent than niacin against human HCA2 (pEC 50 value of 7.5 compared to 6.7 for niacin), has good activity versus the rat orthologue of HCA2 (pEC 50 value of 6.9 compared to 6.4 for niacin) in membranes prepared from Chinese hamster ovary cellsexpressing recombinant human HCA2. GSK256073 (100 μM) suppresses cAMP elevation induced by isoprenaline (100 nM) in rat primary adipocytes. MCE has not independently confirmed the accuracy of these methods. They are for reference only.In VivoGSK256073 (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 inhibition 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. 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. MCE has not independently confirmed the accuracy of these methods. They are for reference only. Animal Model: SD ratDosage: 1, 30 and 100 mg/kg Administration: Oral adminstration Result: Inhibited NEFA expression as a dose-dependent manner. Animal Model: Guinea pigsDosage: 10 mg/kg Administration: Intravenous injection Result: Had the antilipolytic and flushing effects as a HCA2 agonist.Form:SolidIC50& Target:IC50: GPR109A (G-protein coupled receptor 109A),HCA2 (hydroxy-carboxylic acid receptor 2). Specification: 0.99 Molecular Formula: C10H13ClN4O2 Molecular Weight: 256.69 EC Number: 629-897-2 PubChem CID: 46215799 Isomeric SMILES: CCCCCN1C2=C(C(=O)NC1=O)NC(=N2)Cl