WARNING: This product is for research use only, not for human or veterinary use.
MedKoo CAT#: 300120
CAS#: 945667-22-1 (hydrate)
Description: Saxagliptin, also known as BMS-477118, is a new oral hypoglycemic (anti-diabetic drug) of the new dipeptidyl peptidase-4 (DPP-4) inhibitor class of drugs. Saxagliptin was approved in 2008 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.
MedKoo Cat#: 300120
Name: Saxagliptin hydrate
CAS#: 945667-22-1 (hydrate)
Chemical Formula: C18H27N3O3
Exact Mass: 315.19468
Molecular Weight: 333.432
Elemental Analysis: C, 64.84; H, 8.16; N, 12.60; O, 14.39
Related CAS #: 945667-22-1 (hydrate) 709031-78-7 (HCl) 361442-04-8 (free base) 1073057-20-1 (HCl hydrate) 1073057-33-6 (benzoate hydrate)
Synonym: BMS477118; BMS 477118; BMS-477118; Saxagliptin; brand name: Onglyza.
IUPAC/Chemical Name: (1S,3S,5S)-2-((S)-2-amino-2-((1r,3R,5R,7S)-3-hydroxyadamantan-1-yl)acetyl)-2-azabicyclo[3.1.0]hexane-3-carbonitrile hydrate
InChi Key: AFNTWHMDBNQQPX-IGSRIJEQSA-N
InChi Code: InChI=1S/C18H25N3O2.H2O/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,1-7,9,20H2;1H2/t10-,11+,12-,13+,14+,15-,17+,18-;/m1./s1
SMILES Code: N#C[C@H]1N(C([C@@H](N)[C@]23C[C@@]4(O)C[C@](C3)([H])C[C@@](C4)([H])C2)=O)[C@@]5([H])C[C@@]5([H])C1.[H]O[H]
Appearance: Off-white to light yellow solid powder
Purity: >98% (or refer to the Certificate of Analysis)
Shipping Condition: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility: Soluble in DMSO.
Shelf Life: >2 years if stored properly
Drug Formulation: This drug may be formulated in DMSO
Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code: 2934.99.9001
| Biological target: | Saxagliptin is a dipeptidyl peptidase-4 (DPP-4) inhibitor with IC50 of 26 nM. |
| In vitro activity: | To illuminate whether the effects of saxagliptin treatment-induced β-cell proliferation are mediated by SDF-1α-related pathway, in vitro studies were performed after silencing CXCR4, a high-selective SDF-1α receptor, using CXCR4 small interference RNA in INS-1 cell lines (Figure S3 in Supplementary Material). PCNA immunofluorescence staining revealed that 100 nM saxagliptin could increase cell proliferation in INS-1 cells (Figures 5A,B). In addition, saxagliptin increased the p-AKT and active β-catenin protein levels, paralleled with the increase of c-myc and cyclin D1 protein expression (Figures 5C–H). After silencing CXCR4 using RNAi, the above protective effects of saxagliptin were attenuated sharply (Figures 5A–G). Collectively, these data indicate that the SDF-1α/CXCR4 pathway might be responsible for saxagliptin-induced β-cell proliferation. Reference: Front Endocrinol (Lausanne). 2017 Nov 27;8:326. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5711777/ |
| In vivo activity: | To investigate the persistence of the action of saxagliptin on plasma DPP-4 activities, the compound was orally administered to rats and the time course of the inhibition of the plasma DPP-4 activity was evaluated. Saxagliptin inhibited plasma DPP-4 activity by > 95% at 1 h after administration. The inhibitory effects of the drug peaked at 1 h after administration and then returned to baseline at > 40 h after administration (Fig. 2). The renal tissue DPP-4 activity was evaluated at 18 or 40 h after administration. At 18 h after administration, saxagliptin significantly inhibited the renal DPP-4 activity in comparison to the control group. At 40 h after administration, saxagliptin significantly and sustainedly inhibited the renal DPP-4 activity in comparison to the control group. Reference: J Pharmacol Sci. 2017 Nov;135(3):126-130. https://www.sciencedirect.com/science/article/pii/S134786131730172X?via%3Dihub |
| Solvent | Max Conc. mg/mL | Max Conc. mM | |
|---|---|---|---|
| Solubility | |||
| DMSO | 48.5 | 145.46 | |
| Water | 36.5 | 109.47 | |
| Ethanol | 63.0 | 188.95 |
The following data is based on the product molecular weight 333.432 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.
| Concentration / Solvent Volume / Mass | 1 mg | 5 mg | 10 mg |
|---|---|---|---|
| 1 mM | 1.15 mL | 5.76 mL | 11.51 mL |
| 5 mM | 0.23 mL | 1.15 mL | 2.3 mL |
| 10 mM | 0.12 mL | 0.58 mL | 1.15 mL |
| 50 mM | 0.02 mL | 0.12 mL | 0.23 mL |
| Formulation protocol: | 1. Uchii M, Sakai M, Hotta Y, Saeki S, Kimoto N, Hamaguchi A, Kitayama T, Kunori S. The persistent inhibitory properties of saxagliptin on renal dipeptidyl peptidase-4: Studies with HK-2 cells in vitro and normal rats in vivo. J Pharmacol Sci. 2017 Nov;135(3):126-130. doi: 10.1016/j.jphs.2017.10.003. Epub 2017 Oct 23. PMID: 29113790. 2. Li CJ, Sun B, Fang QH, Ding M, Xing YZ, Chen LM, Yu DM. 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. doi: 10.3389/fendo.2017.00326. PMID: 29230196; PMCID: PMC5711777. |
| In vitro protocol: | 1. Uchii M, Sakai M, Hotta Y, Saeki S, Kimoto N, Hamaguchi A, Kitayama T, Kunori S. The persistent inhibitory properties of saxagliptin on renal dipeptidyl peptidase-4: Studies with HK-2 cells in vitro and normal rats in vivo. J Pharmacol Sci. 2017 Nov;135(3):126-130. doi: 10.1016/j.jphs.2017.10.003. Epub 2017 Oct 23. PMID: 29113790. 2. Li CJ, Sun B, Fang QH, Ding M, Xing YZ, Chen LM, Yu DM. 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. doi: 10.3389/fendo.2017.00326. PMID: 29230196; PMCID: PMC5711777. |
| In vivo protocol: | 1. Uchii M, Sakai M, Hotta Y, Saeki S, Kimoto N, Hamaguchi A, Kitayama T, Kunori S. The persistent inhibitory properties of saxagliptin on renal dipeptidyl peptidase-4: Studies with HK-2 cells in vitro and normal rats in vivo. J Pharmacol Sci. 2017 Nov;135(3):126-130. doi: 10.1016/j.jphs.2017.10.003. Epub 2017 Oct 23. PMID: 29113790. 2. Li CJ, Sun B, Fang QH, Ding M, Xing YZ, Chen LM, Yu DM. 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. doi: 10.3389/fendo.2017.00326. PMID: 29230196; PMCID: PMC5711777. |
1: Toth PP. Overview of saxagliptin efficacy and safety in patients with type 2 diabetes and cardiovascular disease or risk factors for cardiovascular disease. Vasc Health Risk Manag. 2014 Dec 23;11:9-23. eCollection 2015. Review. PubMed PMID: 25565858; PubMed Central PMCID: PMC4278729.
2: Konya H, Yano Y, Matsutani S, Tsunoda T, Ikawa T, Kusunoki Y, Matsuo T, Miuchi M, Katsuno T, Hamaguchi T, Miyagawa J, Namba M. Profile of saxagliptin in the treatment of type 2 diabetes: focus on Japanese patients. Ther Clin Risk Manag. 2014 Jul 11;10:547-58. doi: 10.2147/TCRM.S46076. eCollection 2014. Review. PubMed PMID: 25050065; PubMed Central PMCID: PMC4103926.
3: Panagoulias GS, Doupis J. Clinical utility in the treatment of type 2 diabetes with the saxagliptin/metformin fixed combination. Patient Prefer Adherence. 2014 Feb 15;8:227-36. doi: 10.2147/PPA.S34089. eCollection 2014. Review. PubMed PMID: 24627627; PubMed Central PMCID: PMC3931578.
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6: Scheen AJ. Saxagliptin plus metformin combination in patients with type 2 diabetes and renal impairment. Expert Opin Drug Metab Toxicol. 2012 Mar;8(3):383-94. doi: 10.1517/17425255.2012.658771. Epub 2012 Feb 8. Review. PubMed PMID: 22313172.
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9: Scheen AJ. Metformin + saxagliptin for type 2 diabetes. Expert Opin Pharmacother. 2012 Jan;13(1):139-46. doi: 10.1517/14656566.2012.642867. Review. PubMed PMID: 22149373.
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12: McFarland MS, Brock M, Ryals C. Place in therapy for liraglutide and saxagliptin for type 2 diabetes. South Med J. 2011 Jun;104(6):426-39. doi: 10.1097/SMJ.0b013e318215fc7a. Review. PubMed PMID: 21886033.
13: Kania DS, Gonzalvo JD, Weber ZA. Saxagliptin: a clinical review in the treatment of type 2 diabetes mellitus. Clin Ther. 2011 Aug;33(8):1005-22. doi: 10.1016/j.clinthera.2011.06.016. Epub 2011 Jul 28. Review. PubMed PMID: 21802144.
14: Gautier JF, Sauvanet JP. Efficacy of saxagliptin as an add-on to oral monotherapy in the phase 3 clinical development program: predictive factors of the treatment response in type 2 diabetes. Ann Endocrinol (Paris). 2011 Sep;72(4):287-95. doi: 10.1016/j.ando.2011.05.005. Epub 2011 Jul 21. Review. PubMed PMID: 21777901.
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20: LaSalle JR. Reaching HbA1c goals with saxagliptin in combination with other oral antidiabetic drugs. Postgrad Med. 2010 Jan;122(1):144-52. doi: 10.3810/pgm.2010.01.2108. Review. PubMed PMID: 20107298.
