SR3335-ML-176-DataSheet-生命科学试剂-MedChemExpress

1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemESR3335Cat. No.: HY-14413CAS No.: 293753-05-6Synonyms: ML 176分式: CHFNOS分量: 405.34作靶点: ROR作通路: Metabolic Enzyme/Protease储存式: Powder -20C 3 years4C 2 yearsIn solvent -80C 6 months-20C 1 month溶解性数据体外实验 DMSO : 100 mg/mL (246.71 mM)*

2、means soluble, but saturation unknown.Mass Solvent1 mg 5 mg 10 mg Concentration制备储备液1 mM 2.4671 mL 12.3353 mL 24.6706 mL5 mM 0.4934 mL 2.4671 mL 4.9341 mL10 mM 0.2467 mL 1.2335 mL 2.4671 mL请根据产品在不同溶剂中的溶解度，选择合适的溶剂配制储备液，并请注意储备液的保存式和期限。体内实验请根据您的实验动物和给药式选择适当的溶解案，配制前请先配制澄的储备液，再依次添加助溶剂(为保证实验结果的可靠性，体内实验的作液

3、，建议您现现配，当天使；澄的储备液可以根据储存条件，适当保存；以下溶剂前的百分指该溶剂在您配制终溶液中的体积占)：1. 请依序添加每种溶剂： 10% DMSO 40% PEG300 5% Tween-80 45% salineSolubility: 2.5 mg/mL (6.17 mM); Clear solution2. 请依序添加每种溶剂： 10% DMSO 90% (20% SBE-CD in saline)Solubility: 2.5 mg/mL (6.17 mM); Clear solution1/3 Master of Small Molecules 您边的抑制剂师www.Med

4、ChemE3. 请依序添加每种溶剂： 10% DMSO 90% corn oilSolubility: 2.5 mg/mL (6.17 mM); Clear solutionBIOLOGICAL ACTIVITY物活性 SR3335选择性的 ROR 反向激动剂，可直接结合ROR，Ki为220 nM。IC50 & Target Ki: 220 nM (ROR) 1体外研究 SR3335 is a selective ROR partial inverse agonist. In a biochemical radioligand binding assay using 3H25-hydroxyc

5、holesterol as a label it is clear that unlabeled SR3335 dose-dependently competes for binding to theROR LBD. The Ki is calculated as 220 nM using the Cheng-Prusoff equation. In a cell-based chimericreceptor Gal4 DNA-binding domain-NR ligand binding domain cotransfection assay, SR3335 significantlyin

6、hibits the constitutive transactivation activity of ROR (IC50=480 nM)(partial inverse agonist activity), buthas no effect on the activity of LXR and ROR 1.体内研究 Pharmacokinetic studies indicate that SR3335 displays reasonable exposure following an i.p. injection intomice. The ability of SR3335 is ass

7、essed to suppress gluconeogenesis using a diet induced obesity (DIO)mouse model where the mice where treated with 15 mg/kg b.i.d., i.p. for 6-days followed by a pyruvatetolerance test. SR3335 treated mice displays lower plasma glucose levels following the pyruvate challengeconsistent with suppressio

8、n of gluconeogenesis. Importantly, mice treated with SR3335 displayed nodifference in body weight or food intake after 7-days of treatment with SR3335 1.PROTOCOLCell Assay 1 HEK293 cells are maintained in Dulbeccos modified Eagles medium (DMEM) supplemented with 10% fetalbovine serum at 37C under 5%

9、 CO2. HepG2 cells are maintained and routinely propagated in minimumessential medium supplemented with 10% fetal bovine serum at 37C under 5% CO2. 24 h prior totransfection, cells are plated in 96-well plates at a density of 15103 cells/well. Transfections are performedusing LipofectamineTM 2000. 16

10、 h post-transfection, the cells are treated with vehicle or SR3335. 24 h post-treatment, the luciferase activity is measured using the Dual-GloTM luciferase assay system. The valuesindicated represent the meansS.E. from four independently transfected wells. The experiments arerepeated at least three

11、 times 1.MCE has not independently confirmed the accuracy of these methods. They are for reference only.Animal Mice 1Administration 1 30 week old Diet induced obese (DIO) C57BL/6 male mice are purchased from Jackson Laboratories that aremaintained on a 65% Kcal high-fat diet from weaning. DIO mice a

12、re treated twice per day (07:00h and18:00h) with 15 mg/kg SR3335 or vehicle for 6 days i.p. Pyruvate tolerance test is conducted on day 6 of thetreatment. Food is removed from mice in the morning after SR3335 injection, fasted for 6 hours and thepyruvate tolerance test is conducted at 13:00h. Time 0

13、 blood glucose is measured taken from the tail nip andthe pyruvate challenge is initiated by injection of 2g/kg of pyruvate i.p. followed by measuring blood glucose2/3 Master of Small Molecules 您边的抑制剂师www.MedChemEat 15, 30 and 60 min following the injection. Blood glucose is measured by one touch ul

14、tra glucose-meter.MCE has not independently confirmed the accuracy of these methods. They are for reference only. J Pineal Res. 2019 Sep;67(2):e12581. Immunol Lett. 2019 Jul 18. pii: S0165-2478(19)30251-2.See more customer validations on HYPERLINK / www.MedChemEREFERENCES1. Kumar N, et al. Identification of SR3335 (ML-176): a synthetic ROR selective inverse agonist. ACS Chem Biol. 2011 Mar 1