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50mg | ||
100mg |
Saxagliptin HCl (also known as BMS-477118; brand name: Onglyza) is a potent, orally bioactive, selective and reversible DPP4 (dipeptidyl peptidase-4) 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. 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.
ln Vitro |
Treatment with saxagliptin (100 nM; 48 hours; INS-1 832/13 cells) markedly increased the proliferation of S β cells [1]. Treatment with saxagliptin (100 nM; 48 hours; INS-1 832/13 cells) raises the levels of p-AKT and active β-catenin proteins, as well as the production of c-myc and cyclin D1 [1]. In order to increase insulin secretion and decrease glucagon secretion, saxagliptin inhibits the breakdown of glucagon-like peptide-1 [3].
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ln Vivo |
Saxagliptin (1 mg/kg) was administered for 12 weeks to diabetic rats fed a high-fat diet and stimulated with streptozotocin. This resulted in a notable increase in the pancreatic insulin secretory capacity measured by hyperglycemic clamp, as well as an increase in the ratio between the β-cell and α-cell area [1]. In Han-Wistar rats, saxagliptin dose-dependently suppresses plasma DPP-4 activity; approximately 70% inhibition occurs 7 hours after 1 mg/kg administration, and approximately 90% inhibition occurs 7 hours after 10 mg/kg administration. Twenty-four hours after injection, the inhibitory effect was still present at about 20% and 70%, respectively [2].
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Cell Assay |
Cell viability assay [1]
Cell Types: INS-1 832/13 Cell Tested Concentrations: 100 nM Incubation Duration: 48 hrs (hours) Experimental Results: Dramatically induced β-cell proliferation. Western Blot Analysis[1] Cell Types: INS-1 832/13 Cell Tested Concentrations: 100 nM Incubation Duration: 48 hrs (hours) Experimental Results: p-AKT and active β-catenin protein levels increased, while c-myc and cyclin increased D1 protein Express. |
References |
[1]. Chun-Jun Li, et al. Saxagliptin Induces β-Cell Proliferation through Increasing Stromal Cell-Derived Factor-1α In Vivo and In Vitro. Front Endocrinol (Lausanne). 2017 Nov 27;8:326.
[2]. Darshan J Dave. Saxagliptin: A dipeptidyl peptidase-4 inhibitor in the treatment of type 2 diabetes mellitus. J Pharmacol Pharmacother. 2011 Oct;2(4):230-5. [3]. Carolyn F Deacon, et al. Saxagliptin: a new dipeptidyl peptidase-4 inhibitor for the treatment of type 2 diabetes. Adv Ther. 2009 May;26(5):488-99. |
Molecular Formula |
C18H26CLN3O2
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Molecular Weight |
351.875
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CAS # |
709031-78-7
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Related CAS # |
Saxagliptin;361442-04-8;Saxagliptin hydrate;945667-22-1
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Appearance |
Typically exists as solids (or liquids in special cases) at room temperature
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SMILES |
[H]Cl.N#C[C@H]1N(C([C@H]([C@]2(C[C@@H](C3)C4)C[C@]4(O)C[C@@H]3C2)N)=O)[C@@]5([H])C[C@@]5([H])C1
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InChi Key |
TUAZNHHHYVBVBR-IGSRIJEQSA-N
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InChi Code |
InChI=1S/C18H25N3O2.ClH/c19-8-13-2-12-3-14(12)21(13)16(22)15(20)17-4-10-1-11(5-17)7-18(23,6-10)9-17/h10-15,23H,1-7,9,20H21H/t10-,11+,12-,13+,14+,15-,17+,18-/m1./s1
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Chemical Name |
(1S,3S,5S)-2-((2S)-Amino(3-hydroxytricyclo(3.3.1.13,7)dec-1-yl)acetyl)2-
azabicyclo(3.1.0)hexane-3-carbonitrile hydrochloride
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HS Tariff Code |
2934.99.9001
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Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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Solubility (In Vitro) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
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Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80: Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 :Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400  (Please use freshly prepared in vivo formulations for optimal results.) |
Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
1 mM | 2.8419 mL | 14.2094 mL | 28.4188 mL | |
5 mM | 0.5684 mL | 2.8419 mL | 5.6838 mL | |
10 mM | 0.2842 mL | 1.4209 mL | 2.8419 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration: mg/mL;
Method for preparing DMSO stock solution: mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation::Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O,mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.