Anle138b-DataSheet-生命科学试剂-MedChemExpress

1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemEAnle138bCat. No.: HY-101855CAS No.: 882697-00-9分式: CHBrNO分量: 343.17作靶点: Others作通路: Others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 : 50 mg/mL (145.70 mM)H2O : 40% PEG300 5% Tween-80 45%

2、 salineSolubility: 2.5 mg/mL (7.29 mM); Clear solution2. 请依序添加每种溶剂： 10% DMSO 90% corn oilSolubility: 2.5 mg/mL (7.29 mM); Clear solution1/2 Master of Small Molecules 您边的抑制剂师www.MedChemEBIOLOGICAL ACTIVITY物活性 Anle138b种新型低聚物调节剂。体外研究 Oligomeric aggregates are presumed to be the key neurotoxic agent. An

3、le138b blocksthe formation ofpathological aggregates of prion protein and of -synuclein, which is deposited in Parkinsons disease andother synucleinopathies such as dementia with Lewy bodies and multiple system atrophy. Anle138b stronglyinhibits all prion strains tested including BSE-derived and hum

4、an prions. Anle138b shows structure-dependent binding to pathological aggregates and strongly inhibits formation of pathological oligomers bothfor prion protein and -synuclein 1.体内研究 Anle138b has no detectable toxicity at therapeutic doses and an excellent oral bioavailability andbloodbrain-barrier

5、penetration. In mouse models of prion disease and in three different PD mouse models,anle138b strongly inhibits oligomer accumulation, neuronal degeneration, and disease progression 1. Di-phenyl-pyrazole anle138b binds to aggregated tau and inhibits tau aggregation. Anle138b treatmenteffectively ame

6、liorates disease symptoms, increases survival time and improves cognition of tau transgenicPS19 mice 2.PROTOCOLKinase Assay 1 Compounds (Anle138b) are diluted into the assay mixture from 10-fold stock solutions containing 10 %DMSO (v/v), resulting in a final concentration of 1 % DMSO in all samples.

7、 Experiments are started bydiluting the 5-fold stock solution of fluorescently labelled -syn in 50 mM Tris-buffer, pH 7.0, containing 1 %DMSO, 10 M FeCl3 and compounds (Anle138b) in concentrations ranging from 1-10 M. Aggregation ismonitored at room temperature for at least 2.5 h in 3-4 independent

8、samples for each experimental group 1.MCE has not independently confirmed the accuracy of these methods. They are for reference only.Animal Mice: During the first 2 weeks of treatment, 2 mg of anle138b dissolved in 10 L DMSO mixed with 200 LAdministration 1 peanut butter are given. After 2 weeks of

9、treatment, the dose is increased to 5 mg in 10 L DMSO/200 Lpeanut butter. At the age of 33 weeks, the dose is increased to 25 mg per day. All mice are monitored dailyfor signs of disease 1.MCE has not independently confirmed the accuracy of these methods. They are for reference only.REFERENCES1. Wag

10、ner J, et al. Anle138b: a novel oligomer modulator for disease-modifying therapy of neurodegenerative diseases such as prion andParkinsons disease. Acta Neuropathol. 2013 Jun;125(6):795-813.2. Wagner J, et al. Reducing tau aggregates with anle138b delays disease progression in a mouse model of tauopathies. ActaNeuropathol. 2015 Nov;130(5):619-31.McePdfHeightCaution: Product has not been fully v