MRS2957
MRS2957 is a selective P2Y6 receptor agonist. MRS2957 activates Gq-coupled purinergic receptors, increasing phospholipase C, inositol trisphosphate, and intracellular calcium, and indirectly activates AMPK via CaMKKβ, thereby promoting P2Y6-dependent glucose uptake and GLUT4 translocation in skeletal muscle cells and adipocytes. MRS2957 can be used for research on type 2 diabetes.
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- No. CAS: 1228271-30-4
- Fòrmula: C19H28N5O20P3
- Peso molecular:739.37
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Almacenamiento:
Please store the product under the recommended conditions in the Certificate of Analysis.
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Actividad biológica
Descripciòn
IC50 & Target
[2]|
P2Y6 Receptor |
AMPK |
In Vitro
MRS2957 (compound 23) (2 mg/mL) has a half-life of 120 h at pH 1.2 and 23 h in the presence of 1321N1 astrocytoma membranes, while acting as a selective and potent hP2Y6 agonist[6].
MRS2957 (compound 120) (10 μM; 30 min) competes with fluorescent agonist 28 for binding to hP2Y6R in 1321N1 astrocytoma cells[7].
MRS2957 (500 nM; 1 h) increases glucose-stimulated insulin secretion in MIN6 cells under 16.7 mM D-Glucose (HY-B0389) conditions, and MRS2957 (HY-108664)-induced insulin secretion is attenuated by AMPK knockdown and P2Y6R knockdown[2].
MRS2957 (30 min) increases GLUT4 membrane recruitment, and MRS2957 increases glucose uptake and AMPK phosphorylation in C2C12 skeletal muscle cells and 3T3-L1 adipocytes; glucose uptake and AMPK phosphorylation are blocked by MRS2578, and GLUT4 recruitment is blocked by MRS2578 or Compound C[3].
MRS2957 (100 nM; 30 min) stimulates glucose uptake in differentiated C2C12 myotubes and 3T3-L1 adipocytes through P2Y6R- and AMPK-dependent signaling pathways[4].
MRS2957 (100 nM; 1 h) induces AMPK phosphorylation in C2C12 myotubes and 3T3-L1 adipocytes[4].
MRS2957 (60 min) increases GLUT4 recruitment to the plasma membrane in C2C12 myotubes and 3T3-L1 adipocytes[4].
MRS2957 (100-500 nM) stimulates glucose uptake in wild-type mouse primary adipocytes via P2Y6R[4].
MRS2957 (100-500 nM) does not stimulate glucose uptake in primary adipocytes from P2Y6R knockout mice[4].
MRS2957 enhances glucose uptake in differentiated 3T3-L1 mouse adipocytes and primary mouse adipocytes through P2Y6R-dependent AMPK phosphorylation and GLUT4 translocation[5].
MRS2957 (500 nM; 2-60 min) activates AMPK in MIN6 cells, increases pAMPK and pACC, and AMPK phosphorylation reaches a maximum at 15 min, and this response depends on P2Y6R and glucose[2].
MRS2957 (500 nM) activates the P2Y6R-dependent AMPK/ACC signaling pathway in MIN6 β-pancreatic cells, and this activation is blocked by MRS2578[3].
MRS2957 (5 μM; 24 h) promotes the proliferation of NRK-49F rat kidney fibroblasts[1].
MRS2957 (5 μM; 24 h) promotes the migration of NRK-49F rat renal fibroblasts in the scratch assay[1].
MRS2957 (10 μM; 24 h) upregulates the expression of proliferation and pro-fibrotic/myofibroblast marker genes in NRK-49F fibroblasts[1].
MRS2957 (10 μM; 72 h) increases fibronectin and vimentin levels in NRK-49F rat kidney fibroblasts[1].
MRS2957 (500 nM; 15-60 min) induces AMPK phosphorylation in MIN6 cells through intracellular Ca2+ and CaMKKβ signaling pathways, as BAPTA-AM, STO-609, CaMKKβ siRNA, and 2-APB attenuate this response, whereas PI3K, PKC, and L-type Ca2+ channel pathways are not required[2].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:NRK-49F rat renal fibroblasts
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Concentration:5 μM
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Incubation Time:24 h
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Result:Incubation of NRK-49F cells with MRS2957 for 24 h significantly increased cell proliferation compared to controls.
Blockade of the P2Y6R with MRS2578 or chelation of intracellular calcium with BAPTA-AM abolished the effect.
Individual points represented single nuclei; n=4 independent biological experiments.
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Cell Line:NRK-49F rat renal fibroblasts
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Concentration:5 μM
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Incubation Time:24 h
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Result:Promoted the migration of NRK-49F rat renal fibroblasts in the scratch assay.
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Cell Line:NRK-49F rat renal fibroblasts
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Concentration:10 μM
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Incubation Time:24 h
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Result:P2Y6R activation by MRS2957 increased expression of genes encoding the proliferation marker MKI67 and the pro-fibrotic markers PDGFRβ, αSMA, fibronectin, vimentin, and collagen 1 in NRK-49F cells.
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Cell Line:NRK-49F rat renal fibroblasts
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Concentration:10 μM
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Incubation Time:72 h
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Result:Incubation with MRS2957 for 72 h increased abundance of fibronectin and vimentin at the protein level.
Quantification from n=3 independent biological experiments with five technical replicates showed increased expression of both markers.
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Cell Line:MIN6 mouse pancreatic β-cells
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Concentration:500 nM
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Incubation Time:2, 5, 15, 30, 60 min
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Result:Induced a significant increase in AMPK-α phosphorylation.
The increase was rapid and reached maximal stimulation of approximately 2- to 3-fold at 15 min after exposure.
Also significantly increased phosphorylation of ACC, a downstream marker of AMPK activity, compared with controls.
Pre-incubation with MRS2578 significantly decreased AMPK phosphorylation compared with MIN6 cells exposed only to MRS2957, showing that MRS2957-induced AMPK phosphorylation is dependent on P2Y6R activation.
Between 5.5 mM and 16.7 mM glucose, there was a significant increase in phosphorylation of AMPK by P2Y6R.
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Cell Line:MIN6 mouse pancreatic β-cells
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Concentration:500 nM
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Incubation Time:1 h (MRS2957); 1 h (3.3 mM glucose pre-incubation); 48 h (cell culture); 48 h (siRNA)
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Result:Significantly increased glucose-stimulated insulin secretion compared with control cells exposed to glucose alone.
Pre-incubation with P2Y6R antagonist MRS2578 significantly decreased insulin secretion induced by MRS2957.
Varying concentrations of MRS2957 (100 nM-10 μM) significantly increased insulin secretion in the presence of 16.7 mM glucose; 500 nM was the lowest concentration to achieve peak effect.
A significant difference between control and MRS2957-exposed MIN6 cells was observed only at high glucose concentration (16.7 mM).
In AMPK-gene-silenced MIN6 cells, MRS2957-enhanced insulin secretion was significantly lower than in control cells.
There was a significant difference in insulin secretion subsequent to MRS2957 exposure between control and P2Y6R siRNA MIN6 cells.
In MRS2957-exposed groups, insulin secretion was similar in P2Y6R siRNA and AMPK siRNA groups.
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Cell Line:differentiated C2C12 myotubes
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Concentration:100 nM
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Incubation Time:1 h
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Result:Resulted in significant phosphorylation of AMPK in C2C12 myotubes and 3T3-L1 adipocytes.
Chemical Information
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No. CAS 1228271-30-4
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Peso molecular 739.37
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Fòrmula C19H28N5O20P3
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SMILES
O[C@@H]1[C@H](O)[C@@H](COP(OP(OP(OC[C@H]([C@@H](O)[C@H]2O)O[C@H]2N(C(N3)=O)C=CC3=O)(O)=O)(O)=O)(O)=O)O[C@H]1N(C(N/4)=O)C=CC4=N\OC
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Envío
Room temperature in continental US; may vary elsewhere.
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Almacenamiento
Please store the product under the recommended conditions in the Certificate of Analysis.
Pureza y Documentación
Referencias
[3]. Jacobson KA, et al. John Daly Lecture: Structure-guided drug design for adenosine and P2Y receptors.
[6]. Maruoka H, et al. Pyrimidine ribonucleotides with enhanced selectivity as P2Y(6) receptor agonists: novel 4-alkyloxyimino, (S)-methanocarba, and 5'-triphosphate gamma-ester modifications. Journal of medicinal chemistry. 2010 Jun 10;53(11):4488-501. [Content Brief]
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)