SR1078 - ROR Agonist - 生命科學(xué)試劑 - MedChemExpress

1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemESR1078Cat. No.: HY-14422CAS No.: 1246525-60-9分式: CHFNO分量: 431.25作靶點(diǎn): ROR作通路: Metabolic Enzyme/Protease儲(chǔ)存式: Powder -20C 3 years4C 2 yearsIn solvent -80C 6 months-20C 1 month溶解性數(shù)據(jù)體外實(shí)驗(yàn) DMSO : 33.33 mg/mL (77.29 mM; Need ultrasonic)

2、Mass Solvent1 mg 5 mg 10 mg Concentration制備儲(chǔ)備液1 mM 2.3188 mL 11.5942 mL 23.1884 mL5 mM 0.4638 mL 2.3188 mL 4.6377 mL10 mM 0.2319 mL 1.1594 mL 2.3188 mL請根據(jù)產(chǎn)品在不同溶劑中的溶解度，選擇合適的溶劑配制儲(chǔ)備液，并請注意儲(chǔ)備液的保存式和期限。體內(nèi)實(shí)驗(yàn) 請根據(jù)您的實(shí)驗(yàn)動(dòng)物和給藥式選擇適當(dāng)?shù)娜芙獍?，配制前請先配制澄清的?chǔ)備液，再依次添加助溶劑(為保證實(shí)驗(yàn)結(jié)果的可靠性，體內(nèi)實(shí)驗(yàn)的作液，建議您現(xiàn)現(xiàn)配，當(dāng)天使；澄清的儲(chǔ)備液可以根據(jù)儲(chǔ)存條件，適當(dāng)保存；以下溶劑

3、前的百分 指該溶劑在您配制終溶液中的體積占)：1. 請依序添加每種溶劑： 10% DMSO 40% PEG300 5% Tween-80 45% salineSolubility: 2.5 mg/mL (5.80 mM); Suspended solution; Need ultrasonic2. 請依序添加每種溶劑： 10% DMSO 90% (20% SBE-CD in saline)Solubility: 2.5 mg/mL (5.80 mM); Clear solution3. 請依序添加每種溶劑： 10% DMSO 90% corn oilSolubility: 2.5 mg/mL

4、(5.80 mM); Clear solution1/3 Master of Small Molecules 您邊的抑制劑師www.MedChemEBIOLOGICAL ACTIVITY物活性 SR1078種視 酸受體相關(guān)孤受體 (ROR/ROR) 激動(dòng)劑。IC50 & Target ROR/ 1體外研究 SR1078 is a synthetic ROR/ROR ligand. SR1078 modulates the conformation of ROR in a biochemicalassay and activates ROR and ROR driven transcriptio

5、n. Furthermore, SR1078 stimulates expression ofendogenous ROR target genes in HepG2 cells that express both ROR and ROR. In a cell-based chimericreceptor Gal4 DNA-binding domain-NR ligand binding domain cotransfection assay, SR1078 significantlyinhibits the constitutive transactivation activity of R

6、OR and ROR, but has no effect on the activity of FXR,LXR and LXR. In a ROR cotransfection assay, treatment of cells with SR1078 (10 M) results in asignificant increase in transcription. Similarly, in the ROR cotransfection assay, SR1078 treatment results ina stimulation of ROR-dependent transcriptio

7、n activity 1.體內(nèi)研究 The pharmacokinetic properties of SR1078 are examined in mice and noted significant exposure. Plasmaconcentrations reach 3.6 M 1h after a 10 mg/kg i.p. injection of SR1078 and sustained levels of above 800nM even 8h after the single injection. These levels are sufficient to perform

8、 a proof-of-principle experiment todetermine if SR1078 treatment would stimulate ROR target gene expression in an animal model. Mice aretreated with SR1078 (10 mg/kg i.p.) and 2h after the injection the livers are harvested and mRNA purified forassessment of G6Pase and FGF21 gene expression.T he exp

9、ression of both FGF21 and G6Pase issignificantly stimulated by SR1078 treatment vs. vehicle control 1.PROTOCOLKinase Assay 1 The ALPHA screen assays are performed. Assays are performed in triplicate in white opaque 384-well platesunder green light conditions ( 1.MCE has not independently confirmed t

10、he accuracy of these methods. They are for reference only.Cell Assay 1 HEK293 cells are maintained in Dulbeccos modified Eagles medium (DMEM) supplemented with 10% (v/v)fetal bovine serum at 37C under 5% CO2. HepG2 cells are maintained and routinely propagated in minimumessential medium supplemented

11、 with 10% (v/v) fetal bovine serum at 37C under 5% CO2. In experimentswhere lipids and sterols are depleted, cells are maintained on charcoal treated serum (10% (v/v) fetal bovineserum) and treated with 7.5 M lovastatin and 100 M mevalonic acid. 24 h prior to transfection, HepG2 orHEK293 cells are p

12、lated in 96-well plates at a density of 15103 cells/well. Transfections are performedusing 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. Theexperiments

13、 are repeated at least three times 1.MCE has not independently confirmed the accuracy of these methods. They are for reference only.Animal Mice 1Administration 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 ta

14、ken. In the 2h time point liver is taken for target gene analysis. Plasma is2/3 Master of Small Molecules 您邊的抑制劑師www.MedChemEgenerated using standard centrifugation techniques, and the plasma and tissues are frozen at 80C. Plasmaand tissues are mixed with acetonitrile (1:5 (v/v) or 1:5 (w/v), respec

15、tively), sonicated with a probe tipsonicator, 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.戶使本產(chǎn)品發(fā)表的科研獻(xiàn) Acta Pharm Sin B. 2018, 53(1): 62-67. FASEB J. 2019 Apr;33(4):5704-5715. J Cell Physiol. 2019 Feb 27. Immunol Lett. 2019 Jul 18. pii: S0165-2478(19)30251-2.See more customer validations on HYPERLINK / www.MedChemEREFERENCES1. Wang Y, et al. Identification of SR1078, a synthetic agonist for the orphan nuclear receptors ROR and ROR. AC