GRK2 modulator 1
GRK2 modulator 1 is an orally active, brain-penetrant and selective GRK2 modulator. GRK2 modulator 1 enhances the active, non-phosphorylated GRK2 and prevents mitochondrial GRK2 and TOMM6 aggregation. GRK2 modulator 1 enhances the non-amyloidogenic processing of APP and prevent PHF-tau, neurodegeneration, and neuronal loss. GRK2 modulator 1 decreases the senescence marker, UPAR, reduces the Alzheimer disease (AD)-related mortality, and prolongs survival. GRK2 modulator 1 exerts neuroprotection by inhibiting HDAC6, and counteracts age-related cardiac dysfunction. GRK2 modulator 1 can be used for research on AD.
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- No. CAS: 2234900-83-3
- Fòrmula: C21H17NO5
- Peso molecular:363.36
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Almacenamiento:
Please store the product under the recommended conditions in the Certificate of Analysis.
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Actividad biológica
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Chemical Information
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Actividad biológica
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HDAC6 |
GRK2 |
GRK2 modulator 1 (CPD10) interacts with non-phosphorylated GRK2 and phospho-S670-GRK2 in brain lysates from AD mice[1].
GRK2 modulator 1 enhances the active, non-phosphorylated GRK2 and prevents mitochondrial GRK2 and TOMM6 aggregation in a cellular AD model of primary cortical neurons[1].
GRK2 modulator 1 prevents the Aβ1-42-induced mitochondrial dysfunction, as measured by ACO2 activity, with an EC50 value of 155.6 nM[1].
GRK2 modulator 1 inhibits the phospho-S670-GRK2 with an IC50 value of 2.2 μM, whereas only a high concentration of >100 μM affects the kinase activity of wild-type GRK2[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
GRK2 modulator 1 (8 mg/kg/d; p.o.; daily for 8 weeks) retards neurodegenerative PHF-tau hyperphosphorylation and neuronal loss in male Tg2576 mice by chronic unpredictable mild stress (CUMS)[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:Tg2576 mice (12 months old) were used for an AD model[1].
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Dosage:2.7 mg/kg/d; 8 mg/kg/d; 24 mg/kg/d
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Administration:p.o.; daily for 6 months
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Result:Largely prevented dysfunctional GRK2 and TOMM6 aggregated on hippocampal mitochondria and improved the mitochondrial function with higher mitochondrial ACO2 activities and ATP levels than untreated, 18- and 12-month-old Tg2576 mice.
Significantly up-regulated transcripts related to nervous system development.
Induced neurogenesis, which was documented by the increased neuronal marker, NeuN.
Reduced the inflammatory gliosis response, as reflected by the reduced astrocyte marker, Gfap.
Increased the AD protective and Aβ-clearing microglia marker, Cx3cr1.
Shifted the APP-processing activities toward the non-amyloidogenic route.
Strongly reduced hippocampal Aβ plaques, insoluble and soluble Aβ, and mitochondrial Aβ in a dose-dependent manner.
Protected from the increased Aβ-related mortality.
Significantly reduced hippocampal contents of the senescence marker, UPAR.
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Animal Model:Tg2576 mice (male; 14 months old) were received 2 months of chronic unpredictable mild stress to mimic environmental stress[1].
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Dosage:8 mg/kg/d
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Administration:p.o.; daily for 8 weeks
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Result:Prevented the CUMS-enhanced PHF-tau.
Maintained inhibitory phosphorylation of the tau kinase, GSK3B, at serine-9.
Retarded the CUMS-induced neuronal loss and improved the spatial memory of CUMS-subjected Tg2576 mice in the Morris water maze test.
Reduced the CUMS-induced mitochondrial phospho-S670-GRK2 aggregates, which was triggered by increased PHF-tau.
Chemical Information
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No. CAS 2234900-83-3
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Peso molecular 363.36
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Fòrmula C21H17NO5
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SMILES
O=C1C(C(C2CC2)=O)=C(O)C(C3=CC=CC=C3)N1C4=CC=C(OCO5)C5=C4
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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
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
GRK2 modulator 1 Related Classifications
HY-183057 Related Classifications
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