| Description | Saxagliptin (BMS-477118) is a selective and reversible DPP4 inhibitor with IC50 of 26 nM. |
| In vitro | Saxagliptin的DPP4抑制常数Ki为1.3 nM，比维格列汀或西格列汀（另外两种DPP4抑制剂）的Ki（分别为13和18 nM）高出10倍。此外，Saxagliptin对DPP4的特异性远高于DPP8或DPP9酶（分别为400倍和75倍）。Saxagliptin的活性代谢物的效力比原药低两倍。Saxagliptin及其代谢物对于防止DPP4的选择性极高（>4000倍）。[2] Saxagliptin通过减少胰高血糖素样肽-1的降解，从而增强其作用，并与改善β细胞功能和抑制胰高血糖素分泌有关。[3] |
| In vivo | Saxagliptin在Zuckerfa/fa大鼠的葡萄糖波动中产生的最大反应与血浆中DPP4的抑制大约60%相比于对照组有关，而在更高的抑制百分比下未见额外的降糖效果。在0.13-1.3 mg/kg剂量范围内，相对于对照组，Saxagliptin在ob/ob小鼠中显著且依剂量递增地提高葡萄糖清除率。Saxagliptin剂量依赖性地在口服葡萄糖耐量测试(oGTT)后15分钟显著提升血浆胰岛素水平，并在oGTT后60分钟伴随葡萄糖清除曲线的改善。[4] |
| Target activity | DPP4:26 nM |
| Synonyms | BMS-477118, 沙克列汀, Onglyza, 沙格列汀 |
| molecular weight | 315.41 |
| Molecular formula | C18H25N3O2 |
| CAS | 361442-04-8 |
| Storage | store at low temperature | Powder: -20°C for 3 years | In solvent: -80°C for 1 year | Shipping with blue ice. |
| Solubility | DMSO: 35 mg/mL (110.97 mM), Sonication is recommended. H2O: 58 mg/mL (183.9 mM) Ethanol: 23 mg/mL (72.9 mM) |
| References | 1. Tahrani AA, et al. Adv Ther. 2009, 26(3), 249-262. 2. Richter B, et al. Vasc Health Risk Manag. 2008, 4(4), 753-768. 3. Deacon CF, et al. Adv Ther. 2009, 26(5), 488-499. 4. Augeri DJ, et al. J Med Chem. 2005, 48(15), 5025-5037. |