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GSK4112

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Chemical Structure| 1216744-19-2 同义名 : SR6452
CAS号 : 1216744-19-2
货号 : A820682
分子式 : C18H21ClN2O4S
纯度 : 99%+
分子量 : 396.888
MDL号 : MFCD12912412
存储条件：

粉末 Keep in dark place,Sealed in dry,2-8°C

液体 -20°C:3-6个月-80°C:12个月
溶解度 :

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
动物实验配方：
生物活性
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].
实验方案
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
参考文献

[1]Kojetin D, Wang Y, et al. Identification of SR8278, a synthetic antagonist of the nuclear heme receptor REV-ERB. ACS Chem Biol. 2011 Feb 18;6(2):131-4.

[2]Grant D, Yin L, et al. GSK4112, a small molecule chemical probe for the cell biology of the nuclear heme receptor Rev-erbα. ACS Chem Biol. 2010 Oct 15;5(10):925-32.

[3]Grant D, Yin L, Collins JL, et al. GSK4112, a small molecule chemical probe for the cell biology of the nuclear heme receptor Rev-erbα. ACS Chem Biol. 2010;5(10):925‐932