| Size | Price | Stock | Qty |
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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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MBX-2982 (SAR-260093) is a novel, potent, selective and orally bioavailable G protein-coupled receptor 119 (GPR119) agonist with the potential for treating type 2 diabetes. Preclinical evidence suggests that MBX-2982 is a strong, selective, oral GPR119 agonist with a special dual mode of action. It first increases insulin secretion by acting directly on the beta cell. Furthermore, the release of the incretin GLP-1 from the gut is stimulated by MBX-2982. With the potential to reduce weight and improve islet health, this dual action is distinctive and may provide better glucose homeostasis than current diabetes therapies.
| Targets |
GPR119
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|---|---|
| ln Vitro |
MBX-2982 (1 μM) sheared cells in "Chronic Elution/Wash" resulted in a significant increase in cAMP accumulation as measured by IBMX inclusions when compared to control experimental cells (P<0.01; ANOVA; n=3-6). With pEC50s of 8.67±0.11 and 8.93±0.17, respectively, AR-231,453 produced sustained responses (1.82-fold change) across the concentration range observed with acute stimulation. Similar to this, MBX-2982 showed a greater but less severe change in the concentration response (57.54-fold), with acute and sustained pEC50 values of 8.79±0.12 and 7.03±0.13, respectively [1].
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| ln Vivo |
In order to investigate the physiological relevance of the findings in GLUTag and primary enterocytes, 10 mg/kg of the GPR119 agonist MBX-2982 was administered to C57BL/6 mice. In this experiment, DPP-IV was used to preserve active GLP-1 in blood samples; however, DPP-IV twins were not combined in order to examine direct GPR119 effects. Licenseed MBX-2982 embryos showed an increase in GLP-1 levels without an excess of oxidant, suggesting that GPR119-mediated GLP-1 is no longer Dock-dependent [2].
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| Enzyme Assay |
The GloSensor 22F plasmid is transfected into HEK-GPR119 cells, and 24–30 hours later, the cells are used to measure dynamiccAMP. PBS washing, Accutase treatment, and then resuspension in culture media are the steps involved in making cell suspensions. After two centrifugations (300 g, 5 min) to pellet the cells, they are resuspended in the assay buffer (Hank's Balanced Salt Solution, pH 7.4), which is supplemented with 20 mM HEPES and 0.01% fatty acid-free BSA. The cells are then counted and diluted to 600,000 cells/mL in buffer. Next, 2% v/v of GloSensor cAMP reagent is added, and the cells and reagent are allowed to equilibrate for two hours at 20°C with periodic mixing. In triplicate, 50 µl/well of cells are added to white-bottomed 384 well plates (30,000 cells/well), and an Envision plate reader is used to measure the baseline luminescence. To achieve the stated final concentration, 5 μL of MBX-2982 is manually added to the assay wells after being severely diluted in DMSO and then diluted 1:100 in assay buffer to obtain ×10 concentrated solution. To find dynamic cAMP changes over time within the same wells, plates are incubated at 20°C and luminescence is measured at regular intervals. The cAMP responses are expressed as fold over control (cells treated with vehicles) at each time point. [1]
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| Cell Assay |
The process of making cell suspensions involves dislodging HEK-GPR119 cells using PBS wash and accutase treatment, then resuspension in culture media. The cells are grown to confluency in flasks. After that, cells are twice washed by pelleting through centrifugation (227g, 7 min, 20°C), and then resuspension in warm assay buffer (Hank's Balanced Salt Solution, pH 7.4, supplemented with 20 mM HEPES and 0.01% fatty acid free BSA). The second wash is followed by a 5-minute incubation at 37°C. Following cell counting, the cells are diluted in warm assay buffer to 200,000 cells/mL[1].
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| Animal Protocol |
Mice: Male C57BL/6 mice are employed. Male 10-week-old mice (n = 20 per group) are fasted for the entire night and given either MBX-2982 at 10 mg/kg or vehicle (15% polyethylene glycol 400+85% of 23.5% hydroxypropyl-β-cyclodextrin) orally. Thirty minutes after compound dosing, half of the animals (n = 10 per group) are killed by CO2 asphyxiation, and blood is extracted by cardiac puncture. In order to maintain active GLP-1, a DPP-IV inhibitor is pre-added to the blood collection tubes (10 µL per 1 mL of blood), and the syringe walls are rinsed with the inhibitor prior to the cardiac puncture. The other half of the animals (n = 10 per group) were put to death for blood collection 10 minutes after the glucose load and received an oral glucose bolus (3 g/kg) 30 minutes after compound dosing. The active GLP-1 (ver 2) kit is used to measure GLP-1 levels in plasma samples.
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| References |
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| Molecular Formula |
C22H24N8OS
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|---|---|
| Molecular Weight |
448.54396
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| Exact Mass |
448.18
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| Elemental Analysis |
C, 58.91; H, 5.39; N, 24.98; O, 3.57; S, 7.15
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| CAS # |
1037792-44-1
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| Appearance |
Solid powder
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| SMILES |
CCC1=CN=C(N=C1)N2CCC(CC2)C3=NC(=CS3)COC4=CC=C(C=C4)N5C=NN=N5
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| InChi Key |
NFTMKHWBOINJGM-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C22H24N8OS/c1-2-16-11-23-22(24-12-16)29-9-7-17(8-10-29)21-26-18(14-32-21)13-31-20-5-3-19(4-6-20)30-15-25-27-28-30/h3-6,11-12,14-15,17H,2,7-10,13H2,1H3
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| Chemical Name |
2-[1-(5-ethylpyrimidin-2-yl)piperidin-4-yl]-4-[[4-(tetrazol-1-yl)phenoxy]methyl]-1,3-thiazole
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| Synonyms |
SAR-260093; SAR 260093; SAR260093; MBX-2982; MBX2982; MBX 2982
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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) |
DMSO: ~50 mg/mL (~111.5 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.75 mg/mL (6.13 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (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 27.5 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.2295 mL | 11.1473 mL | 22.2946 mL | |
| 5 mM | 0.4459 mL | 2.2295 mL | 4.4589 mL | |
| 10 mM | 0.2229 mL | 1.1147 mL | 2.2295 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 |
| NCT04432090 | Active Recruiting |
Drug: Placebo Drug: Study Medication (MBX-2982) |
Diabetes Mellitus, Type 1 | AdventHealth Translational Research Institute |
April 21, 2021 | Phase 2 |
| NCT01035879 | Completed | Drug: MBX-2982 Drug: Sitagliptin Drug: placebo |
Diabetes | CymaBay Therapeutics, Inc. | December 2009 | Phase 2 |
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