| Description |
Anle138b is a novel oligomer modulator.
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| Related Catalog |
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| In Vitro |
Oligomeric aggregates are presumed to be the key neurotoxic agent. Anle138b blocksthe formation of pathological aggregates of prion protein and of α-synuclein, which is deposited in Parkinson’s disease and other synucleinopathies such as dementia with Lewy bodies and multiple system atrophy. Anle138b strongly inhibits all prion strains tested including BSE-derived and human prions. Anle138b shows structure-dependent binding to pathological aggregates and strongly inhibits formation of pathological oligomers both for prion protein and α-synuclein[1].
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| In Vivo |
Anle138b has no detectable toxicity at therapeutic doses and an excellent oral bioavailability and blood–brain-barrier 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 treatment effectively ameliorates disease symptoms, increases survival time and improves cognition of tau transgenic PS19 mice[2].
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| Kinase Assay |
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. Experiments are started by diluting the 5-fold stock solution of fluorescently labelled α-syn in 50 mM Tris-buffer, pH 7.0, containing 1 % DMSO, 10 μM FeCl3 and compounds (Anle138b) in concentrations ranging from 1-10 μM. Aggregation is monitored at room temperature for at least 2.5 h in 3-4 independent samples for each experimental group[1].
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| Animal Admin |
Mice: During the first 2 weeks of treatment, 2 mg of anle138b dissolved in 10 μL DMSO mixed with 200 μL peanut butter are given. After 2 weeks of treatment, the dose is increased to 5 mg in 10 μL DMSO/200 μL peanut butter. At the age of 33 weeks, the dose is increased to 2×5 mg per day. All mice are monitored daily for signs of disease[1].
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| References |
[1]. Wagner J, et al. Anle138b: a novel oligomer modulator for disease-modifying therapy of neurodegenerative diseases such as prion and Parkinson's 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. Acta Neuropathol. 2015 Nov;130(5):619-31.
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