Saxagliptin (BMS-477118)

製品コードS1540 バッチS154001

印刷

化学情報

Chemical Structure Synonyms Onglyza,BMS-477118 Storage
(From the date of receipt)		 3 years -20°C powder
1 years -80°C in solvent
化学式

C18H25N3O2
分子量 315.41 CAS No. 361442-04-8
Solubility (25°C)* 体外 DMSO 63 mg/mL (199.74 mM)
Water 63 mg/mL (199.74 mM)
Ethanol 24 mg/mL (76.09 mM)
* <1 mg/ml means slightly soluble or insoluble.
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.

溶剤液（一定の濃度）を調合する

生物活性

製品説明 Saxagliptin (BMS-477118, Onglyza) is a selective and reversible DPP4 inhibitor with IC50 of 26 nM.
in vitro 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). [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. [3]
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. [4]

プロトコル(参考用のみ)

キナーゼアッセイ In vitro DPP4 inhibition assays
Inhibition of human DPP4 activity is measured under steady-state conditions by following the absorbance increase at 405 nm upon the cleavage of the pseudosubstrate, Gly-Pro-pNA. Assays are performed in 96-well plates using a Thermomax plate reader. Typically reactions contained 100 μL of ATE buffer (100 mM Aces, 52 mM Tris, 52 mM ethanolamine, pH 7.4), 0.45 nM enzyme, either 120 or 1000 μM of substrate (S < Km and S > Km, Km= 180 μM) and variable concentration of the inhibitor. To ensure steady-state conditions for slow-binding inhibitors, enzyme is preincubated with saxagliptin for 40 min prior to substrate addition. All serial inhibitor dilutions are in DMSO and final solvent concentration did not exceed 1%. Inhibitor potency is evaluated by fitting inhibition data to the binding isotherm:  vi/v = range/[1 + (I/IC50)n] + background, where vi is the initial reaction velocity at different concentrations of inhibitor, I; v is the control velocity in the absence of inhibitor; range is the difference between the uninhibited velocity and background; background is the rate of spontaneous substrate hydrolysis in the absent of enzyme; n is the Hill coefficient. Calculated IC50's at each substrate concentration are converted to Ki's by assuming competitive inhibition according to the equation Ki = IC50/[1 + (S/Km)]. All inhibitors are competitive as judged by close agreement of Ki values obtained from assays at high and low substrate concentrations. In cases where IC50 at the low substrate concentration is close to the enzyme concentration used in the assay, the data are fit to the Morrison equation to account for the depletion of the free inhibitor. IC50 values are further refined to determine Ki values to account for the substrate concentration in the assay using Ki = IC50/[1 + (S/Km)].
動物実験 動物モデル Male 13−14 week-old ob/ob mice
投薬量 10 μmol/kg
投与方法 Orally

カスタマーフィードバック

Data from [Data independently produced by , , J Chromatogr B Analyt Technol Biomed Life Sci, 2018, 1081-1082:109-117]

Selleckの高級品が、幾つかの出版された研究調査結果（以下を含む）で使われた：

Simultaneous Estimation of Saxagliptin and Dapagliflozin in Human Plasma by Validated High Performance Liquid Chromatography - Ultraviolet Method [ Turk J Pharm Sci, 2019, 16(2):227-233] PubMed: 32454718
Subversion of Systemic Glucose Metabolism as a Mechanism to Support the Growth of Leukemia Cells. [ Cancer Cell, 2018, 34(4):659-673] PubMed: 30270124
Sensitive analysis and pharmacokinetic study of a novel gemcitabine carbamate prodrug and its active metabolite gemcitabine in rats using LC-ESI-MS/MS [Zhou Y, et al. J Chromatogr B Analyt Technol Biomed Life Sci, 2018, 1083:249-257] PubMed: 29554521
Quantitative determination of metformin, saxagliptin and 5-hydroxy saxagliptin simultaneously by hydrophilic interaction liquid chromatography - electrospray ionization mass spectrometry and its application to a bioequivalence study with a single-pill com䲧盌Ỵ盍㧀盋膉甘 [Peng Y, et al. J Chromatogr B Analyt Technol Biomed Life Sci, 2018, 1081-1082:109-117] PubMed: 29518719
Molecular cloning and biochemical characterization of Xaa-Pro dipeptidyl-peptidase from Streptococcus mutans and its inhibition by anti-human DPP IV drugs. [ FEMS Microbiol Lett, 2016, 363(9)] PubMed: 27010012

長期の保管のために-20°Cの下で製品を保ってください。

人間や獣医の診断であるか治療的な使用のためにでない。

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