Uses
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
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 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[2].GSK256073 (intravenousinjection; 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].
| Animal Model: | SD rat[2] |
| Dosage: | 1, 30 and 100 mg/kg |
| Administration: | Oral adminstration |
| Result: | Inhibited NEFA expression as a dose-dependent manner. |
| Animal Model: | Guinea pigs[2] |
| Dosage: | 10 mg/kg |
| Administration: | Intravenousinjection |
| Result: | Had the antilipolytic and flushing effects as a HCA2 agonist. |
References
[1] Dobbins RL, et al. GSK256073, a selective agonist of G-protein coupled receptor 109A (GPR109A) reduces serum glucose in subjects with type 2 diabetes mellitus.Diabetes Obes Metab.2013 Nov;15(11):1013-21. DOI:
10.1111/dom.12132[2] Sprecher D, et al. Discovery and characterization of GSK256073, a non-flushing hydroxy-carboxylic acid receptor 2 (HCA2) agonist.Eur J Pharmacol. 2015 Jun 5;756:1-7. DOI:
10.1016/j.ejphar.2015.01.051
