1037792-44-1
1037792-44-1 structure
- Name: MBX-2982
- Chemical Name: 2-[1-(5-ethylpyrimidin-2-yl)piperidin-4-yl]-4-[[4-(tetrazol-1-yl)phenoxy]methyl]-1,3-thiazole
- CAS Number: 1037792-44-1
- Molecular Formula: C22H24N8OS
- Molecular Weight: 448.544
- Catalog: Signaling Pathways GPCR/G Protein GPR119
- Create Date: 2017-11-28 18:54:06
- Modify Date: 2024-01-30 14:53:53
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MBX-2982 is a selective, orally-available G protein-coupled receptor 119 (GPR119) agonist.
| Name | 2-[1-(5-ethylpyrimidin-2-yl)piperidin-4-yl]-4-[[4-(tetrazol-1-yl)phenoxy]methyl]-1,3-thiazole |
|---|---|
| Synonyms |
CS-0745
Pyrimidine, 5-ethyl-2-[4-[4-[[4-(1H-tetrazol-1-yl)phenoxy]methyl]-2-thiazolyl]-1-piperidinyl]- MBX 2982 UNII-B5TRY67L51 5-Ethyl-2-[4-(4-{[4-(1H-tetrazol-1-yl)phenoxy]methyl}-1,3-thiazol-2-yl)-1-piperidinyl]pyrimidine cc-550 MBX-2982 |
| Description | MBX-2982 is a selective, orally-available G protein-coupled receptor 119 (GPR119) agonist. |
|---|---|
| Related Catalog | |
| Target |
GPR119[1] |
| In Vitro | In cells pre-treated with MBX-2982 (1 µM) in “chronic incubation/washout” experiments, cAMP accumulation captured by IBMX inclusion is significantly increased compared to control cells (P<0.01; ANOVA; n=3-6) despite extensive washing to remove excess agonist. AR-231,453 produces sustained responses in a similar concentration range to those observed with acute stimulation (a small 1.82 fold shift), with pEC50s of 8.67±0.11 and 8.93±0.17, respectively. Likewise, a large but less severe shift in concentration responses (57.54 fold) is observed for MBX-2982 with respective sustained and acute pEC50s of 7.03±0.13 and 8.79±0.12[1]. |
| In Vivo | To examine whether the observations in GLUTag and the primary intestinal cells has physiological relevance, C57BL/6 mice are treated with the GPR119 agonist MBX-2982 at a dose of 10 mg/kg. Note that in order to examine a direct GPR119 effect, no DPP-IV inhibitor is co-administered in this experiment, but a DPP-IV inhibitor is used to preserve active GLP-1 in the blood samples. The plasma GLP-1 levels from the mice dosed with MBX-2982 are increased without a glucose load, indicating that GPR119-mediated GLP-1 secretion is not dependent on glucose[2]. |
| Kinase Assay | HEK-GPR119 cells are transfected with GloSensor 22F plasmid and used for dynamic cAMP measurements 24-30 h later. Cell suspensions are made by dislodging the cells using PBS wash and Accutase treatment followed by resuspension in culture media. Cells are then washed twice by pelleting through centrifugation (300g, 5 min) and resuspension in assay buffer (Hank's Balanced Salt Solution supplemented with 20 mM HEPES and 0.01% fatty acid free BSA, pH 7.4). Cells are then counted and diluted to 600,000 cells/mL in buffer, before GloSensor cAMP reagent is added (2% v/v) and equilibrated with the cells for 2 h at 20°C with periodic mixing. 50 µl/well of cells are added to white-bottomed 384 well plates (30,000 cells/well) in triplicate and baseline luminescence is measuring using an Envision plate-reader. 5 μL of MBX-2982 (serially diluted in DMSO and then diluted 1:100 in assay buffer to obtain ×10 concentrated solution) is manually added to the assay wells to achieve the stated final concentration. Plates are incubated at 20°C with luminescence read at regular intervals to detect dynamic cAMP changes over time within the same wells. cAMP responses at each time-point are expressed as fold over control (vehicle-treated cells)[1]. |
| Cell Assay | HEK-GPR119 cells are grown to confluency in flasks, and cell suspensions are made by dislodging cells using PBS wash and accutase treatment followed by resuspension in culture media. Cells are then washed twice by pelleting through centrifugation (227g, 7 min, 20°C) and resuspension in warm assay buffer (Hank's Balanced Salt Solution supplemented with 20 mM HEPES and 0.01% fatty acid free BSA, pH 7.4), with a 5 min incubation at 37°C after the second wash. Cells are then counted and diluted to 200,000 cells/mL in warm assay buffer[1]. |
| Animal Admin | Mice[2] C57BL/6 male mice are used. Overnight fasted, 10 week-old male mice (n=20 per group) are given either vehicle (15% polyethylene glycol 400+85% of 23.5% hydroxypropyl-β-cyclodextrin) or MBX-2982 at 10 mg/kg via oral gavage. Half of the animals (n=10 per group) are killed by CO2 asphyxiation 30 min after compound dosing, and blood is collected by cardiac puncture. To preserve active GLP-1, a DPP-IV inhibitor (10 µL per 1 mL of blood) is pre-added to the blood collection tubes and, before the cardiac puncture, the walls of the syringes are rinsed with the DPP-IV inhibitor. The other half of the animals (n=10 per group) received a bolus of oral glucose (3 g/kg) 30 min after compound dosing, and are killed for blood collection 10 min after the glucose load. GLP-1 levels in the plasma samples are measured using the active GLP-1 (ver 2) kit. |
| References |
| Density | 1.4±0.1 g/cm3 |
|---|---|
| Boiling Point | 683.6±65.0 °C at 760 mmHg |
| Molecular Formula | C22H24N8OS |
| Molecular Weight | 448.544 |
| Flash Point | 367.3±34.3 °C |
| Exact Mass | 448.179382 |
| PSA | 122.98000 |
| LogP | 3.88 |
| Vapour Pressure | 0.0±2.1 mmHg at 25°C |
| Index of Refraction | 1.739 |
| Storage condition | -20°C |