| Identification | Back Directory | [Name]
SR8278 | [CAS]
1254944-66-5 | [Synonyms]
SR8278
SR8278;SR-8278;SR 8278
UIEBLUZPSFAFOC-UHFFFAOYSA-N
ethyl2-(5-methylsulfanylthiophene-2-carbonyl)-3,4-dihydro-1H-isoquinoline-3-carboxylate
Ethyl 1,2,3,4-tetrahydro-2-[[5-(methylthio)-2-thienyl]carbonyl]-3-isoquinolinecarboxylate
1,2,3,4-Tetrahydro-2-[[5-(methylthio)-2-thienyl]carbonyl]-3-isoquinolinecarboxylic acid ethyl ester
3-Isoquinolinecarboxylic acid, 1,2,3,4-tetrahydro-2-[[5-(methylthio)-2-thienyl]carbonyl]-, ethyl ester | [Molecular Formula]
C18H19NO3S2 | [MDL Number]
MFCD18782736 | [MOL File]
1254944-66-5.mol | [Molecular Weight]
361.48 |
| Chemical Properties | Back Directory | [Melting point ]
52-55°C | [Boiling point ]
535.7±50.0 °C(Predicted) | [density ]
1.32±0.1 g/cm3(Predicted) | [storage temp. ]
2-8°C | [solubility ]
DMSO: ≥30mg/mL | [form ]
film | [pka]
-3.20±0.40(Predicted) | [color ]
white to tan | [InChI]
1S/C18H19NO3S2/c1-3-22-18(21)14-10-12-6-4-5-7-13(12)11-19(14)17(20)15-8-9-16(23-2)24-15/h4-9,14H,3,10-11H2,1-2H3 | [InChIKey]
UIEBLUZPSFAFOC-UHFFFAOYSA-N | [SMILES]
CCOC(=O)C1Cc2ccccc2CN1C(=O)c3ccc(SC)s3 |
| Hazard Information | Back Directory | [Description]
REV-ERBα is a nuclear receptor and transcription repressor that coordinates circadian rhythm and metabolic pathways in a heme-dependent manner. SR8278 is an antagonist of REV-ERBα (EC50 = 0.47 μM), blocking activation of the receptor by the synthetic agonist GSK 4112 . Moreover, SR8278 stimulates the expression of two REV-ERBα target genes involved in the regulation of glucose production, glucose 6-phosphatase and phosphoenolpyruvate carboxykinase, in liver cells. SR8278 has been used, with GSK 4112, to elucidate the role of REV-ERBα in regulating glucagon secretion in pancreatic alpha cells. | [Uses]
SR 8278 is a synthetic antagonist of the nuclear heme receptor REV-ERB. | [in vivo]
SR8278 (slow microinjection; 20 μg/mouse) exerts antidepressant and anxiolytic effects in a circadian time-dependent manner in 6-OHDA-lesioned mice and restores the circadian rhythm of mood-related behaviors[1].
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SR8278 (slow microinjection; 20 μg/mouse) restores the binding activities of REV-ERBα and NURR1 to the tyrosine hydroxylase promoter and the induction of enrichment of the R/N motif, recognized by REV-ERBα and NURR1[1]. | Animal Model: | 6-OHDA-lesioned mice[1] | | Dosage: | 20 μg/mouse | | Administration: | slow microinjection; 20 μg/mouse | | Result: | Recovered mood-related behavioral deficits shown in 6-OHDA-lesioned mice.
Altered remaining DAergic neuron specific transcription levels of REV-ERBα and Nurr1 in the VTA.
Restored antagonistic crosstalk of REV-ERBα and NURR1 binding activity to TH promoter and TH protein levels in VTA.
Induced enrichments of REV-ERBα and NURR1 binding motifs at dawn.
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| [storage]
Store at +4°C | [References]
[1] HéLèNE DUEZ Bart S. Rev-erb-alpha: an integrator of circadian rhythms and metabolism.[J]. Journal of applied physiology, 2009, 107 6: 1972-1980. DOI: 10.1152/japplphysiol.00570.2009
[2] DOUGLAS KOJETIN. Identification of SR8278, a Synthetic Antagonist of the Nuclear Heme Receptor REV-ERB[J]. ACS Chemical Biology, 2010, 6 2: 131-134. DOI: 10.1021/cb1002575
[3] ELAINE VIEIRA. Involvement of the clock gene Rev-erb alpha in the regulation of glucagon secretion in pancreatic alpha-cells.[J]. PLoS ONE, 2013: e69939. DOI: 10.1371/journal.pone.0069939 |
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