product name Saxagliptin
Description: Saxagliptin, also known as BMS-477118, is a orally active, selective and reversible DPP4 inhibitor with IC50 of 26 nM. Saxagliptin was approved in 2008 by FDA for the treatment of type 2 diabetes. Saxagliptin is a competitive DPP4 inhibitor that slows the inactivation of the incretin hormones, thereby increasing their bloodstream concentrations and reducing fasting and postprandial glucose concentrations in a glucose-dependent manner in patients with type 2 diabetes mellitus.
References: Adv Ther. 2009 Mar;26(3):249-62; J Med Chem. 2005 Jul 28;48(15):5025-37.
315.41
Formula
C18H25N3O2
CAS No.
361442-04-8
Storage
-20℃ for 3 years in powder form
-80℃ for 2 years in solvent
Solubility (In vitro)
DMSO: 63 mg/mL (199.7 mM)
Water: 2 mg/mL (5.89 mM)
Ethanol: 24 mg/mL (76.1 mM)
Solubility (In vivo)
Saline: 30 mg/mL
Synonyms
BMS-477118
other peoduct :References PubMed ID：:http://www.ncbi.nlm.nih.gov/pubmed/19414865
| In Vitro |
In vitro activity: 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 Ki 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). 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. Kinase Assay: Cell Assay: |
|---|---|
| In Vivo | Maximal responses of Saxagliptin in glucose excursion in Zuckerfa/fa rats are associated with plasma DPP4 inhibition of approximately 60% vs. control, and no additional antihyperglycemic effects are seen at higher percent inhibition. Saxagliptin is highly effective at eliciting marked dose-dependent enhancements in glucose clearance in the dose range 0.13-1.3 mg/kg in ob/ob mice relative to controls. Saxagliptin dose-dependently elevate plasma insulin significantly at 15 min post-oGTT, with concomitant improvement in the glucose clearance curves at 60 min post-oGTT. |
| Animal model | Male 13−14 week-old ob/ob mice |
| Formulation & Dosage | Dissolved in water; 10 μmol/kg; p.o. administration |
| References | Adv Ther. 2009 Mar;26(3):249-62; J Med Chem. 2005 Jul 28;48(15):5025-37. |
