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5mg |
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10mg |
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25mg |
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50mg |
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100mg |
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250mg |
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500mg |
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1g |
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Other Sizes |
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Purity: ≥98%
Omarigliptin (formerly known as MK-3102; MK3102) is a potent, selective, oral and long-acting DPP-4 (dipeptidyl peptidase 4) inhibitor with antidiabetic properties. At a 1.6 nM IC50, it inhibits DPP-4. Omarigliptin exhibits high selectivity (IC50 > 67 μM) against all proteases tested. At IKr, Caγ1.2, and Naγ1.5, its ion channel activity is weak (IC50 > 30 μmol/L). Furthermore, in every assay within an extensive selectivity counterscreen comprising 168 radioligand binding or enzymatic assays, an IC50 > 10 μmol/L was achieved. Under hyperglycemia, omarigliptin binds quickly and competitively to the DPP-4 active site. This process is highly selective and reversible, resulting in elevated insulin and decreased glucagon levels. It is presently undergoing a phase 3 clinical trial and has good pharmacokinetic profiles appropriate for once-weekly dosing.
Targets |
DPP-4 (IC50 = 1.6 nM)
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ln Vitro |
Omarigliptin is a potent DPP-4 inhibitor with weak ion channel activity (IC50 > 30 μmol/L at IKr, Caγ1.2, and Naγ1.5) and strong selectivity over other proteases tested (IC50 > 67 μmol/L). Furthermore, in every assay within an extensive selectivity counterscreen comprising 168 radioligand binding or enzymatic assays, an IC50 > 10 μmol/L was achieved. Under hyperglycemic circumstances, omagliptin binds quickly and competitively to the DPP-4 active site, a reversible and highly selective process that raises insulin levels and lowers glucagon levels[2].
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ln Vivo |
In an oral glucose tolerance test (OGTT), it was given orally to lean mice one hour before the dextrose challenge. It significantly decreased blood glucose excursion in a dose-dependent manner, going from 0.01 mg/kg (7% reduction in glucose AUC) to 0.3 mg/kg (51% reduction). Plasma concentrations of active GLP-1 are dose-dependently increased upon omarigliptin administration. The male Sprague-Dawley rat and beagle dog exhibit low plasma clearance (0.9−1.1 mL/min/kg), 0.8−1.3 L/kg at steady state for the volume of distribution, and a long terminal half-life (∼11−22 h) in relation to the pharmacokinetics of omarigliptin. Omaligliptin has a good oral bioavailability in both dogs and rats (approximately 100%). Throughout the course of the trial, omajiptin is well tolerated; no death or adverse physical symptoms are observed[1]. After volunteers received a single oral dose of 25 mg, omarigliptin was absorbed quickly, reaching peak concentrations (Cmax) of 750 nmol/L in less than one hour (Tmax). The estimated bioavailability was 74%[2].
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Enzyme Assay |
Omarigliptin is a potent DPP-4 inhibitor with weak ion channel activity (IC50 > 30 μmol/L at IKr, Caγ1.2, and Naγ1.5) and strong selectivity over other proteases tested (IC50 > 67 μmol/L). Furthermore, in every assay within an extensive selectivity counterscreen comprising 168 radioligand binding or enzymatic assays, an IC50 > 10 μmol/L was achieved. Under hyperglycemic circumstances, omagliptin binds quickly and competitively to the DPP-4 active site, a reversible and highly selective process that raises insulin levels and lowers glucagon levels.
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Animal Protocol |
12 weeks, C57BL/6 male mice
2.5, 5 mg/kg P.o.; once a week for 8 weeks (50 mg/kg streptozotocin (STZ); i.p.; daily for five days) |
References |
Molecular Formula |
C17H20F2N4O3S
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Molecular Weight |
398.43
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Exact Mass |
398.12
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Elemental Analysis |
C, 51.25; H, 5.06; F, 9.54; N, 14.06; O, 12.05; S, 8.05
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CAS # |
1226781-44-7
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Related CAS # |
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Appearance |
White to off-white solid powder
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SMILES |
CS(=O)(=O)N1C=C2CN(CC2=N1)[C@@H]3C[C@@H]([C@H](OC3)C4=C(C=CC(=C4)F)F)N
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InChi Key |
MKMPWKUAHLTIBJ-ISTRZQFTSA-N
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InChi Code |
InChI=1S/C17H20F2N4O3S/c1-27(24,25)23-7-10-6-22(8-16(10)21-23)12-5-15(20)17(26-9-12)13-4-11(18)2-3-14(13)19/h2-4,7,12,15,17H,5-6,8-9,20H2,1H3/t12-,15+,17-/m1/s1
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Chemical Name |
(2R,3S,5R)-2-(2,5-difluorophenyl)-5-(2-methylsulfonyl-4,6-dihydropyrrolo[3,4-c]pyrazol-5-yl)oxan-3-amine
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Synonyms |
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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 |
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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) |
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Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (6.27 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (6.27 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C,1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.5 mg/mL (6.27 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
1 mM | 2.5099 mL | 12.5493 mL | 25.0985 mL | |
5 mM | 0.5020 mL | 2.5099 mL | 5.0197 mL | |
10 mM | 0.2510 mL | 1.2549 mL | 2.5099 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.
NCT Number | Recruitment | interventions | Conditions | Sponsor/Collaborators | Start Date | Phases |
NCT02906709 | Completed | Drug: Omarigliptin Drug: Placebo |
Type 2 Diabetes Mellitus | Merck Sharp & Dohme LLC | October 17, 2016 | Phase 4 |
NCT01814748 | Completed | Drug: Omarigliptin Drug: Metformin |
Diabetes Mellitus | Merck Sharp & Dohme LLC | May 3, 2013 | Phase 3 |
NCT01697592 | Completed | Drug: Matching placebo to omarigliptin Drug: Omarigliptin |
Type 2 Diabetes Mellitus | Merck Sharp & Dohme LLC | October 24, 2012 | Phase 3 |
NCT01717313 | Completed | Drug: Placebo to Omarigliptin Drug: Omarigliptin |
Type 2 Diabetes Mellitus | Merck Sharp & Dohme LLC | December 5, 2012 | Phase 3 |
NCT01703221 | Completed | Drug: Sitagliptin Drug: Omarigliptin |
Type 2 Diabetes Mellitus | Merck Sharp & Dohme LLC | October 24, 2012 | Phase 3 |
Superposition of sitagliptin and fluoroomarigliptin in the DPP-4 active site using their cocrystal structures of DPP-4 (PDB codes1X70and4PNZ).J Med Chem.2014 Apr 24;57(8):3205-12. th> |
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Improvement of metabolic stability.J Med Chem.2014 Apr 24;57(8):3205-12. td> |
Formation of pyrrolopyrimidine metabolite.J Med Chem.2014 Apr 24;57(8):3205-12. td> |