Omarigliptin, also called MA-3102, is an selective inhibitor of DPP-4 with IC50 of 1.6 nM and Ki of 0.8 nM. Its selectivity is higher than other 168 proteasomes.
Omarigliptin is a competitive, potent and selective inhibitor of dipeptidyl peptidase 4 (DPP-4) (IC50 = 1.6 nM, Ki = 0.8 nM) developed for the treatment of type 2 diabetes, which is highly selective over all proteases tested (IC50 > 67 μM). Omarigliptin has weak ion channel activity (IC50 > 30 μM at IKr, Cav1.2, and Nav1.5)[3]. Omarigliptin is indicated to have favorable effects on glycosylated hemoglobin (HbA1c), fasting and postmeal plasma glucose[4]. Omarigliptin improves glucose control in patients with type 2 diabetes by increasing the circulating concentration of glucagon-like peptide 1 and glucose-dependent insulinotropic polypeptide. Administration of omarigliptin dose-dependently increased plasma concentrations of active GLP-1, with maximal increases in active GLP-1 observed at the 0.3 to 1 mg/kg doses[3]. Omarigliptin resulted in ∼2-fold increases in weighted average postprandial active GLP-1. The average renal clearance of omarigliptin was ∼2 L/h and DPP-4 inhibition ranged from ∼77% to 89% at 168 hours [5].When orally administered 1 h prior to dextrose challenge, omarigliptin significantly reduced blood glucose excursion in a dose-dependent manner from 0.01 mg/kg (7% reduction in glucose AUC) to 0.3 mg/kg (51% reduction) in lean mice[3]. The oral bioavailability of omarigliptin was good in both dogs and rats (∼100%),and the mean percentage of unbound omarigliptin (1, 10, and 100 μM) in CD-1 mouse, Sprague–Dawley rat, beagle dog, and human plasma was 38%, 15%, 43%, and 68%, respectively[3].
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