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描述 | Rev-erbα (NR1D1) and Rev-erbβ (NR1D2) are heme sensors and atypical members of the nuclear receptor superfamily. Many of the Rev-erbα target genes play important roles in regulation of metabolic processes. In addition, Rev-erbα regulates the expression of proteins that comprise the core circadian clock in mammals. GSK4112 is a functional Rev-erbα agonist in liver cells to inhibit expression of the circadian target gene bmal1 with EC50 value of 0.4 μM. In the presence of 0.5 μM hemin, recruitment of the NCoR1 ID1 peptide was reduced. In contrast, 10 μM GSK4112 increased the interaction of the receptor with the peptide above the basal level, consistent with the data from the chemical array screening. Following saturation of the receptor with hemin, the tertiary amine GSK4112 was able to reverse the suppression of the FRET (fluorescence resonance energy transfer) signal. The competitive actions of hemin and GSK4112 in the FRET assay strongly suggested that their binding as ligands to Rev-erbα was mutually exclusive. In the presence of 10 μM GSK4112, a statistically significant repression of bmal1 expression was observed. The mRNA for g6pc, pepck, and pgc1a were all repressed by 10 μM GSK4112 in HepG2 cells. A ChIP experiment in the same cells showed that a doubling of HDAC3 recruitment was observed in the presence of GSK4112 demonstrating that GSK4112 performed as a Rev-erbα agonist in cells to promote the formation of a transcriptional repressor complex with HDAC3 and repress target genes associated with the pathway of gluconeogenesis[3]. |
计算器 | ||||
存储液制备 | 1mg | 5mg | 10mg | |
1 mM 5 mM 10 mM |
2.52mL 0.50mL 0.25mL |
12.60mL 2.52mL 1.26mL |
25.20mL 5.04mL 2.52mL |
CAS号 | 1216744-19-2 |
分子式 | C18H21ClN2O4S |
分子量 | 396.888 |
别名 | SR6452 |
运输 | 蓝冰 |
存储条件 |
In solvent -20°C:3-6个月-80°C:12个月 Pure form Keep in dark place,Sealed in dry,2-8°C |
溶解方案 |
DMSO: 25 mg/mL(62.99 mM),配合低频超声助溶,注意:DMSO长时间开封后,会吸水并导致溶解能力下降,请避免使用长期开封的DMSO 以下溶解方案都请先按照体外实验的方式配制澄清的储备液,再依次添加助溶剂: ——为保证实验结果的可靠性,澄清的储备液可以根据储存条件,适当保存;体内实验的工作液,建议现用现配,当天使用; 以下溶剂前显示的百分比是指该溶剂在终溶液中的体积占比;如在配制过程中出现沉淀、析出现象,可以通过加热和/或超声的方式助溶
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动物实验配方 |