Tarenflurbil-R-Flurbiprofen-DataSheet-生命科学试剂-MedChemExpress

1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemETarenflurbilCat. No.: HY-10291CAS No.: 51543-40-9Synonyms: (R)-Flurbiprofen; MPC7869分式: CHFO分量: 244.26作靶点: RAR/RXR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

2、 : 50 mg/mL (204.70 mM)* means soluble, but saturation unknown.Mass Solvent1 mg 5 mg 10 mg Concentration制备储备液1 mM 4.0940 mL 20.4700 mL 40.9400 mL5 mM 0.8188 mL 4.0940 mL 8.1880 mL10 mM 0.4094 mL 2.0470 mL 4.0940 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，配制前请先配制澄清的储备液，再依

3、次添加助溶剂(为保证实验结果的可靠性，体内实验的作液，建议您现现配，当天使；澄清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 (10.23 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 (10.23 mM); Clear solution1/3 Master of

4、Small Molecules 您边的抑制剂师www.MedChemE3. 请依序添加每种溶剂： 10% DMSO 90% corn oilSolubility: 2.5 mg/mL (10.23 mM); Clear solutionBIOLOGICAL ACTIVITY物活性 Tarenflurbil (R)-Flurbiprofen)是Flurbiprofen 的 R 型对映体，Tarenflurbil (R)-Flurbiprofen) 抑制 3H9-cis-RA 结合到 RXR LBD，IC50 为 75 M。IC50 & Target IC50: 75 M (RXR) 1体外研究

5、Tarenflurbil (R)-Flurbiprofen) can significantly reduce A secretion, but at the same time, increases the levelof intracellular A. The binding between 3H9-cis-RA and RXR is competitively inhibited by both unlabeled(R)-Flurbiprofen and 9-cis-RA. (R)-Flurbiprofen can interfere with the interaction betw

6、een RXR and 9-cis-retinoid acid (9-cis-RA), and that 9-cis-RA decreases Tarenflurbil (R)-Flurbiprofen)s reduction of Asecretion. Tarenflurbil (R)-Flurbiprofen) treatment significantly increases the levels of intracellular A species1. The well characterized, nonsteroidal anti-inflammatory drug (nonst

7、eroidal anti-inflammatory drug),Tarenflurbil (R)-Flurbiprofen) affects only A and not Notch formation, indicating that second generationGSMs and nonsteroidal anti-inflammatory drug-based GSMs have different modes of action regarding Notchprocessing 2.体内研究 Effects of the early and late onset of treat

8、ment with Tarenflurbil (R)-Flurbiprofen) are assessed in C57BL6/Jmice that develop a non-remitting form of the disease, and in SJL mice that develop a relapsing-remitting(RR)-EAE. Tarenflurbil (R)-Flurbiprofen) completely prevents the development of clinical EAE scores inC57BL6/J mice when the treat

9、ment is started within 3 days after immunization. This regimen is referred to aspreventive treatment. The effect is dose-dependent, and the minimum daily dose for complete prevention is 5mg/kg/day. Effects of Tarenflurbil (R)-Flurbiprofen) are comparable to those of Fingolimod (FTY720, 0.5mg/kg/day)

10、, which is used as the positive control. Tarenflurbil (R)-Flurbiprofen) also significantly reducesclinical EAE scores in C57BL6/J mice when treatment is started shortly before onset of clinicalmanifestations, referred to as semi-therapeutic (10 mg/kg/day) and reduces clinical scores when thetreatmen

11、t is initiated after full development of the disease on day 13 (5 mg/g/day) 3.PROTOCOLCell Assay 2 HEK293 cells stably expressing human FLAG-Notch1-E (FLAG-NE) or APPswe are cultured in Dulbeccosmodified Eagles medium supplemented with 10% fetal bovine serum, nonessential amino acids, 10 MHepes, and

12、 300 g/mL hygromycin or 100 g/mL Zeocin, respectively. For each experiment, the cells arecounted and plated in T75 flasks, 6- or 384-well plates (for N, A, and NICD experiments, respectively) theday before treatment. On the following day, the GSM, Tarenflurbil (R)-Flurbiprofen) (200 M), sulindacsulf

13、ide (125 M), AZ1136 (25 M), AZ4126 (400 nM), or vehicle control (Me2SO) is separately added to freshcell media and incubated for 24, 16, or 5 h (for N, A, and NICD experiments, respectively) beforeconditioned media or cells are analyzed 2.MCE has not independently confirmed the accuracy of these met

14、hods. They are for reference only.2/3 Master of Small Molecules 您边的抑制剂师www.MedChemEAnimal Mice 3Administration 3 Female C57BL6/J and female SJL mice, aged 10-12 weeks at immunization, are used for study of primaryprogressive EAE and relapsing-remitting EAE, respectively. Mice are housed at 3-5 mice

15、per cage atconstant room temperature (211C) under a regular light/dark schedule with light from 7:00 a.m. to 7:00p.m. Food and water are available ad libitum. Animals are treated orally with Tarenflurbil (R)-Flurbiprofen),S-Flurbiprofen or vehicle or FTY720 via the drinking water. FTY720 (fingolimod

16、) is used as the positivecontrol at 0.5 mg/kg/day. The therapy is continuous and started on day 3 after immunization for preventivetreatment, on day 7-8 to allow for some immune activation for analysis, 4 days before onset of clinicalsymptoms for semi-therapeutic treatment (C57BL6/J), on day 13 afte

17、r full development of EAE for late-therapeutic treatment of C57BL6/J mice or after the first peak of the disease 19 days after immunization forlate-therapeutic treatment of SJL mice. For late-therapeutic treatment of C57BL6/J mice that have a primaryprogressive course of the disease and do not recov

18、er, $(R)-Flurbiprofen or vehicle are administered viadrug or vehicle soaked sweet cornflakes to ensure drug, fluid and calories intake during the disease. Theanimals are accustomed to the cornflakes before the start of the therapy. The evaluation of these differenttherapeutic paradigms increases the

19、 predictability of a potential clinical usefulness of Tarenflurbil (R)-Flurbiprofen) in human MS. For thelate treatment, mice are allocated pairwise to vehicle and $(R)-Flurbiprofen groups according to their clinical scores during the first peak so that the scores are identical inboth groups at the

20、onset of treatment. The doses of R-Flurbiprofen are 2.5, 5 and 10 mg/kg in C57BL6/Jmice and 5 mg/kg/day for SJL mice. S-Flurbiprofen is used at 10 mg/kg/day. The purity of R- and S-Flurbiprofen is 99.9%, and the stability in drinking water and food is confirmed by LC-MS/MS analyses forup to 7 days a

21、t room temperature. After this time, recovery of R-Flurbiprofen is 95.7% and of S-Flurbiprofen91.5%. The experiments adhered to the guidelines of the Committee for Research and Ethical Issues of theInternational Association for the Study of Pain (IASP) and to those of GV-SOLAS for animal welfare inscience.MCE has not independently confirmed the accuracy of these met