Saxagliptin, the monohydrate form of anhydrous saxagliptin, is a reversible and selective DPP4 inhibitor with IC50 of 26 nM. It is used for the treatment of type 2 diabetes.
Dipeptidylpeptidase 4 (DPP4) belongs to the S9b gene family of postproline serine peptidases. It acts mostly as a secreted membrane protein, mediating the degradation and inactivation of glucagon-like peptide (GLP)-1 and gastric inhibitory protein (GIP)[3]. Saxagliptin is a selective, reversible inhibitor of dipeptidyl peptidase-4 (DPP-4) approved for the treatment of type 2 diabetes mellitus in adults[4]. Treatment with 15 μM saxagliptin completely abolished the phosphorylation of extracellular-regulated kinase (ERK) induced by fetal bovine serum (FBS), insulin and IGF1. Saxagliptin (1.5 or 15 μM) inhibited type 1 collagen production after 14 days and decreased the formation of nodules of mineralization after 21 days[5]. Saxagliptin 2.5-400 mg daily resulted in measurable intact postprandial plasma GLP-1 concentrations that were 1.5-fold to 3-fold higher than those measured in patients receiving placebo. It also resulted in increased β-cell responsiveness to glucose in both the postprandial and fasting states, increased levels of intact GLP-1 and GIP after oral glucose administration, and decreased postprandial glucagon secretion[4].
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