1. Metabolic Enzyme/Protease
  2. ROR

SR1078 

Cat. No.: HY-14422 Purity: 99.91%
Data Sheet SDS Handling Instructions

SR1078 is an agonist of retinoic acid receptor-related orphan receptor (ROR)α/γ.

For research use only. We do not sell to patients.
SR1078 Chemical Structure

SR1078 Chemical Structure

CAS No. : 1246525-60-9

Size Price Stock Quantity
Free Sample (0.5-1 mg)   Apply now  
10 mM * 1 mL in DMSO $94 In-stock
5 mg $85 In-stock
10 mg $120 In-stock
50 mg $470 In-stock
100 mg $880 In-stock
200 mg   Get quote  
500 mg   Get quote  

* Please select Quantity before adding items.

Featured Recommendations

Related Screening Libraries:

Related Small Molecules:

  • Biological Activity

  • Protocol

  • Technical Information

  • Purity & Documentation

  • References

Description

SR1078 is an agonist of retinoic acid receptor-related orphan receptor (ROR)α/γ.

IC50 & Target

RORα/γ[1]

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].

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].

References
Preparing Stock Solutions
Concentration Volume (DMSO) Mass 1 mg 5 mg 10 mg
1 mM 2.3188 mL 11.5942 mL 23.1884 mL
5 mM 0.4638 mL 2.3188 mL 4.6377 mL
10 mM 0.2319 mL 1.1594 mL 2.3188 mL
Kinase Assay
[1]

The ALPHA screen assays are performed. Assays are performed in triplicate in white opaque 384-well plates under green light conditions (<100 lux) at room temperature. The final assay volume is 20 μL. All dilutions are made in assay buffer (100 mM NaCl, 25 mM Hepes, 0.1% (w/v) BSA, pH 7.4). The final DMSO concentration is 0.25% (v/v). A mix of 12 μL of GST-RORγ-LBD (10 nM), beads (12.5 μg/mL of each donor and acceptor), and 4 μL of increasing concentrations (210 nM-50 μM) of compound SR1078 are added to the wells, the plates are sealed and incubated for 1h. After this preincubation step, 4 μL of Biotin-TRAP220-2 peptide (50 nM) is added, the plates are sealed and further incubated for 2h. The plates are read on PerkinElmer Envision 2104 and data analyzed using GraphPad Prism software[1]. MCE has not independently confirmed the accuracy of these methods. They are for reference only.

Cell Assay
[1]

SR1078 is prepared in DMSO and stored, and then diluted with appropriate medium before use[1].

HEK293 cells are maintained in Dulbecco's modified Eagle's 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]. MCE has not independently confirmed the accuracy of these methods. They are for reference only.

Animal Administration
[1]

SR1078 is prepared in DMSO and diluted with saline or PBS (Mice)[1].

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. MCE has not independently confirmed the accuracy of these methods. They are for reference only.

References
Molecular Weight

431.25

Formula

C₁₇H₁₀F₉NO₂

CAS No.

1246525-60-9

Storage
Powder -20°C 3 years
  4°C 2 years
In solvent -80°C 6 months
  -20°C 1 month
Shipping

Room temperature in continental US; may vary elsewhere

Solvent & Solubility

10 mM in DMSO

* "<1 mg/mL" means slightly soluble or insoluble. "≥" means soluble, but saturation unknown.

Inquiry Online

Your information is safe with us. * Required Fields.

Product name

 

Salutation

Applicant name *

 

Email address *

Phone number

 

Organization name *

Country *

 

Requested quantity *

Remarks

Bulk Inquiry

Inquiry Information

Product Name:
SR1078
Cat. No.:
HY-14422
Quantity: