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ELN484228
本产品不向个人销售,仅用作科学研究,不用于任何人体实验及非科研性质的动物实验。
ELN484228图片
CAS NO:312-63-0
规格:≥98%
包装与价格:
包装价格(元)
5mg电议
10mg电议
25mg电议
50mg电议
100mg电议
250mg电议
500mg电议

产品介绍
理化性质和储存条件
Molecular Weight (MW) 251.28
Formula C12H10FNO2S
CAS No. 312-63-0
Storage-20℃ for 3 years in powder form
-80℃ for 2 years in solvent
Solubility (In vitro)DMSO:>10 mM
Water:
Ethanol:
Chemical Name N-(4-Fluorophenyl)benzenesulfonamide
Synonyms ELN-484228; ELN484228; ELN 484228
SMILES Code O=S(C1=CC=CC=C1)(NC2=CC=C(F)C=C2)=O
实验参考方法
In Vitro

In vitro activity: ELN484228, a phenyl-sulfonamide compound, is a cell-permeable blocker of α-synuclein which is a key protein in Parkinson’s disease. It was identified by a combination of computational and experimental techniques. ELN484228 has substantial biological activity in cellular models of α-synuclein-mediated dysfunction, including rescue of α-synuclein-induced disruption of vesicle trafficking and dopaminergic neuronal loss and neurite retraction most likely by reducing the amount of α-synuclein targeted to sites of vesicle mobilization such as the synapse in neurons or the site of bead engulfment in microglial cells. These results indicate that targeting α-synuclein by small molecules such as ELN484228 represents a promising approach to the development of therapeutic treatments of Parkinson's disease and related conditions.


Kinase Assay: Aggregation of αSyn was assayed in triplicates at 37°C under shaking (300 rpm) in solutions containing 50 μM protein in the absence and presence of tenfold higher concentration of compound ELN484228 in 25 mM Tris buffer pH 7.4, 100 mM NaCl with the addition of 0.01% NaN3. Aliquots were withdrawn on a daily basis and the thioflavin T (ThT) fluorescence signal was recorded after addition of 20 μM of ThT to each aliquot. Fluorescence emission spectra from 460 to 600 nm were then recorded at an excitation wavelength of 446 nm employing a Cary-Eclipse spectrofluorimeter (Varian, Palo Alto CA). Quenching of the ThT fluorescence by the addition of ELN484228 was assayed by incubating pre-formed fibrils with the compound and by comparison of the ThT fluorescence signal before and after the addition of ELN484228, but no significant change in signal was found. The aggregation of αSyn in the presence of ELN484228 was also characterized in the presence of low concentrations of SDS (200 μM) under the same experimental conditions as described above. The time-dependences of the ThT fluorescence signal were fitted to a nucleation-elongation model as previously described. TEM images were obtained using a Philips CEM100 transmission electron microscope. The samples were applied on Formvar-carbon coated nickel grids and stained with 2% (w/v) uranyl acetate.


Cell Assay: Microglia were obtained from cerebral cortices of 1–3 day old neonate mice. A full description of microglia culture methods is provided in the Supporting Information text. Hippocampal neurons were isolated from embryonic day 18 prenatal rat hippocampi and cultured in antibiotic- and serum-free NbActiv4 medium (both from BrainBits, Springfield IL) at 37°C in an atmosphere of 5% CO2, 9% O2 and on glass coverslips coated with poly-lysine. Half of the medium was replaced every 3 to 4 days. Cells were used for the experiments after 21–28 days in vitro.

In VivoA full description of the generation of transgenic animals is provided in the Supporting Information text. Briefly, Bacterial Artificial Chromosome (BAC) clone RP11-458H10, containing the human SNCA gene sequence (Life Technologies, Carlsbad, CA) was modified to generate both the Rep1 mutation and E46K mutation by BAC recombineering methods as described. Circular BAC constructs containing the hSNCA transgene (~168 Kb) were used to perform pronuclear microinjection into B6SJL F2 mouse strains (The Jackson Laboratories, Bar Harbor, ME) in the concentration of 1–3 μg/μl followed by implantation into pseudo pregnant females (Xenogen Biosciences, Cranbury, NJ). Founder animals were bred with B6D2F1 mice and maintained as heterozygotes on this background with non-transgenic littermates as controls. Line BAC-Tg3(SNCAE46K) animals were bred in sufficient numbers for a 3, 8–9, 12–14, 18–20 month old (MO) characterization cohorts and were 3–8 generations from founders. All mice were housed in a pathogen-free, climate controlled and given food and water ad libitum. All animal studies were reviewed and approved by the Institutional Animal Care and Use Committee at Elan pharmaceuticals in accordance with the National Institutes of Health Guide for the Care and Use of Laboratory Animals.
Animal model Mouse
Formulation & Dosage
References PLoS One. 2014 Feb 14;9(2):e87133.