SaxagliptinS1540

Saxagliptin has an inhibition constant Ki of 1.3 nM for DPP4 inhibition, which is 10-fold more potent than either vildagliptin or sitagliptin (another two DPP4 inhibitors) with K_i of 13 and 18 nM. In addition, Saxagliptin demonstrates greater specificity for DPP4 than for either the DPP8 or DPP9 enzymes (400- and 75- fold, respectively). The active metablite of saxagliptin is two-fold less potent than the parent. Both Saxagliptin and its metabolite are highly selective (>4000-fold) for the prevention of DPP4 compared with a range of other proteases (selectivity of sitagliptin and vildagliptin for DPP4 is >2600 and <250-fold, respectively, compared with DPP8 and DPP9). ^[2] Saxagliptin reduces the degradation of the incretin hormone glucagon-like peptide-1, thereby enhancing its actions, and is associated with improved β-cell function and suppression of glucagon secretion