Saxagliptin H2O (BMS-477118, Onglyza) is a selective and reversible DPP4 inhibitor with IC50 of 26 nM.
Saxagliptin H2O (BMS-477118, Onglyza) is a selective and reversible DPP4 inhibitor with IC50 of 26 nM.
In vitro, saxagliptin inhibits FBS-, insulin- and IGF1-induced ERK phosphorylation and cell proliferation, in both MSC and MC3T3E1 preosteoblasts. In the absence of growth factors, saxagliptin has no effect on ERK activation or cell proliferation. In both MSC and MC3T3E1 cells, saxagliptin in the presence of FBS inhibits Runx2 and osteocalcin expression, type-1 collagen production and mineralization, while increasing PPAR-gamma expression[4].
Saxagliptin exerts direct beneficial effects on the arterial wall in an animal model of type 2 diabetes by increasing NO availability and improving antioxidant status. Saxagliptin reverses vascular hypertrophic remodeling and ameliorates NO availability in small arteries from db/db mice through the abrogation of NAD(P)H oxidase-driven eNOS uncoupling and by reducing the action of cyclooxygenase-1-derived vasoconstrictors downregulating the expression of thromboxane-prostanoid receptors[2]. DPP-4 inhibition with saxagliptin also improves pancreatic β-cell function in postprandial and fasting states, and decreases postprandial glucagon concentration[3].
[1] Neumiller JJ, et al. Am J Health Syst Pharm. 2010, 67(18):1515-25. [2] Solini A, et al. Vascul Pharmacol. 2016, 76:62-71. [3] Henry RR, et al. Diabetes Obes Metab. 2011, 13(9):850-8.
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