Saxagliptin-13C-d2 is intended for use as an internal standard for the quantification of saxagliptin by GC- or LC-MS. Saxagliptin is a potent inhibitor of dipeptidyl peptidase 4 (DPP-4; Ki = 0.6 nM).1 It inhibits DPP-4 ex vivo (ED50 = 0.12 μmol/kg) in plasma from normal fasted rats. Saxagliptin (0.3-3 mg/kg) reduces plasma glucose levels in Zuckerfa/fa diabetic rats in a dose-dependent manner. Oral administration at doses ranging from 1-10 μmol/kg increases plasma insulin levels and improves glucose clearance in ob/ob mice, a transgenic model of obesity. Saxagliptin induces systolic and diastolic dysfunction, reduces contractile force, and exacerbates ischemia-reperfusion injury-induced cardiac dysfunction in isolated guinea pig hearts.2 Formulations containing saxagliptin have been used for the treatment of type 2 diabetes.
1.Augeri, D.J., Robl, J.A., Betebenner, D.A., et al.Discovery and preclinical profile of Saxagliptin (BMS-477118): A highly potent, long-acting, orally active dipeptidyl peptidase IV inhibitor for the treatment of type 2 diabetesJ. Med. Chem.48(15)5025-5037(2005) 2.Koyani, C.N., Kolesnik, E., WÖlkart, G., et al.Dipeptidyl peptidase-4 independent cardiac dysfunction links saxagliptin to heart failureBiochem. Pharmacol.145(1)64-80(2017)