中文名称:

SR1078

中文同义词:

N-[4-[2,2,2-三氟-1-羟基-1-(三氟甲基)乙基]苯基]-4-(三氟甲基)苯甲酰胺;RORΑ/Γ激动剂(SR1078);化合物SR 1078

英文名称:

SR 1078

英文同义词:

N-[4-[2,2,2-Trifluoro-1-hydroxy-1-(trifluoromethyl)ethyl]phenyl]-4-(trifluoromethyl)benzamide;SR 1078;SR1078,N-[4-(2,2,2-Trifluoro-1-hydroxy-1-trifluoroMethyl-ethyl)-phenyl]-4-trifluoroMethyl-benzaMide;N-[4-[2,2,2-Trifluoro-1-hydroxy-1-(trifluoromethyl)ethyl]phenyl]-4-(trifluoromethyl)benzamide SR1078;SR1078;SR 1078;SR-1078;N-[4-(1,1,1,3,3,3-Hexafluoro-2-hydroxy-2-propanyl)phenyl]-4-(trifluoromethyl)benzamide;SR1078,N-[4-(2,2,2-TRIFLUORO-1-HYDROXY-1-TRIFLUOROMETHYL-ETHYL)-PHENYL]-4-TRIFLU;SR 1078; SR-1078

CAS号:

1246525-60-9

分子式:

C17H10F9NO2

分子量:

431.25

EINECS号:

相关类别:

蛋白酪氨酸激酶;抑制剂;细胞生物学试剂

Mol文件:

1246525-60-9.mol

熔点 

169℃

沸点 

362.9±42.0 °C(Predicted)

密度 

1.527±0.06 g/cm3(Predicted)

酸度系数(pKa)

9.21±0.15(Predicted)

生物活性

SR1078是RORα/γ的激活剂。

靶点

Target Value RORα () RORγ ()

Target

Value

RORα ()

RORγ ()

体外研究

SR1078 is a synthetic RORα/RORγ ligand. SR1078 modulates the conformation of RORγ in a biochemical assay and activates RORα and RORγ driven transcription. Furthermore, SR1078 stimulates expression of endogenous ROR target genes in HepG2 cells that express both RORα and RORγ. In a cell-based chimeric receptor Gal4 DNA-binding domain-NR ligand binding domain cotransfection assay, SR1078 significantly inhibits the constitutive transactivation activity of RORα and RORγ, but has no effect on the activity of FXR, LXRα and LXRβ. In a RORα cotransfection assay, treatment of cells with SR1078 (10 μM) results in a significant increase in transcription. Similarly, in the RORγ cotransfection assay, SR1078 treatment results in a stimulation of RORγ-dependent transcription activity. SR1078 (2-10 μM; 24 hours) shows a dose-dependent increase in expression of A2BP1, CYP19A1, NLGN1, and IPTR1 in SH-SY5Y cells. EC50’s are in the range of 3-5 μM.

体内研究

The pharmacokinetic properties of SR1078 are examined in mice and noted significant exposure. Plasma concentrations reach 3.6 μM 1h after a 10 mg/kg i.p. injection of SR1078 and sustained levels of above 800 nM even 8h after the single injection. These levels are sufficient to perform a proof-of-principle experiment to determine if SR1078 treatment would stimulate ROR target gene expression in an animal model. Mice are treated with SR1078 (10 mg/kg; i.p.) and 2h after the injection the livers are harvested and mRNA purified for assessment of G6Pase and FGF21 gene expression.T he expression of both FGF21 and G6Pase is significantly stimulated by SR1078 treatment vs. vehicle control. SR1078 (10 mg/kg; i.p.) shows a significant 25% reduction in repetitive grooming behavior in the BTBR mice.