| CAS |
No.1246525-60-9 |
| 英文名称 |
SR1078 |
| 别名 |
;SKI-606;SR1078||SR-1078;SR1078;CS-1045; |
| 分子式 |
C17H10F9NO2 |
| 分子量 |
431.25 |
| 溶解性 |
Soluble in DMSO ≥5mg/mL(Need ultrasonic) |
| 纯度 |
≥98% |
| 外观(性状) |
White to off-white Solid |
| 储存条件 |
Powder:2-8℃，2 years;Insolvent(母液):-20℃，6 months;-80℃，1 year |
| 运输条件 |
冷藏运输 |
| MDL |
MFCD18782737 |
| SMILES |
O=C(NC1=CC=C(C(C(F)(F)F)(C(F)(F)F)O)C=C1)C2=CC=C(C(F)(F)F)C=C2 |
| InChIKey |
DUXWIYXHHGNUJU-UHFFFAOYSA-N |
| InChI |
InChI=1S/C17H10F9NO2/c18-15(19,20)11-3-1-9(2-4-11)13(28)27-12-7-5-10(6-8-12)14(29,16(21,22)23)17(24,25)26/h1-8,29H,(H,27,28) |
| PubChem CID |
17980288 |
| 靶点 |
RORα;RORγ |
| 通路 |
Metabolic Enzyme&Protease |
| 背景说明 |
是一种RORα/RORγ)激动剂。 |
| 生物活性 |
SR1078 is a selective agonist of retinoic acid receptor-related orphan receptor α/γ (RORα/RORγ). SR1078 directly binds to the ligand binding domain of RORα and RORγ and increases the transcriptional activity of these receptors， leading to stimulation of RORα/γ target gene transcription.[1-2] |
| In Vitro |
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[1].?
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[2]. |
| In Vivo |
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[1].?
SR1078 (10 mg/kg; i.p.) shows a significant 25% reduction in repetitive grooming behavior in the BTBR mice[2]. |
| 细胞实验 |
HEK293 cells are maintained in Dulbeccos modified Eagles medium (DMEM) supplemented with 10% (v/v) fetal bovine serum at 37°C under 5% CO2. HepG2 cells are maintained and routinely propagated in minimum essential medium supplemented with 10% (v/v) fetal bovine serum at 37°C under 5% CO2. In experiments where lipids and sterols are depleted， cells are maintained on charcoal treated serum (10% (v/v) fetal bovine serum) and treated with 7.5 μM lovastatin and 100 μM mevalonic acid. 24 h prior to transfection， HepG2 or HEK293 cells are plated in 96-well plates at a density of 15×103 cells/well. Transfections are performed using LipofectamineTM 2000. 16 h post-transfection， the cells are treated with vehicle or SR1078. 24 h post-treatment， the luciferase activity is measured using the Dual-GloTM luciferase assay system. The experiments are repeated at least three times[1]. |
| 动物实验 |
Mice[1] Plasma levels of SR1078 are evaluated in C57BL6 mice (n=3 per time point) administered by i.p. injection. After 1， 2， 4， and 8h blood is taken. In the 2h time point liver is taken for target gene analysis. Plasma is generated using standard centrifugation techniques， and the plasma and tissues are frozen at ?80°C. Plasma and tissues are mixed with acetonitrile (1:5 (v/v) or 1:5 (w/v)， respectively)， sonicated with a probe tip sonicator， and analyzed for drug levels by liquid chromatography/tandem mass spectrometry. |
| 激酶实验 |
The ALPHA screen assays are performed. Assays are performed in triplicate in white opaque 384-well plates under green light conditions ([1]. |
| 数据来源文献 |
[1]. Wang Y， et al. Identification of SR1078， a synthetic agonist for the orphan nuclear receptors RORα and RORγ. ACS Chem Biol. 2010 Nov 19;5(11):1029-34.
[2]. Wang Y， Billon C， Walker JK， Burris TP. Therapeutic Effect of a Synthetic RORα/γ Agonist in an Animal Model of Autism. ACS Chem Neurosci. 2016;7(2):143-148. |
| 规格 |
1mg 5mg 10mg 25mg 50mg |
| 单位 |
瓶 |
中文
英语
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