Anle138b | Protein aggregation inhibitor

Anle138b (882697-00-9) is an aggregation inhibitor that modulates the formation of pathological oligomers of both prion and α-synuclein.¹ In mouse models of prion diseases and Parkinson’s disease, Anle138b strongly inhibited oligomer formation, neuronal degeneration, and disease progression even after disease onset.^1,2 Anle138b has delayed disease progression and prevented motor decline in multiple neurodegenerative models.^3-6 Treatment of melanoma cells with anle138b caused massive cell death via major dysregulation of autophagy revealing a protective effect of α-synuclein on autophagy in these cells.⁷ Orally bioavailable and able to cross the blood-brain barrier.

References/Citations:

1) Wagner et al. (2013), Anle138b: a novel oligomer modulator for disease-modifying therapy of neurodegenerative diseases such as prion and Parkinson’s disease; Acta Neuropathol., 125 795
2) Levin et al. (2014), The oligomer modulator anle138b inhibits disease progression in a Parkinson’s mouse model even with treatment started after disease onset; Acta Neuropathol., 127 779
3) Wagner et al. (2015), Reducing tau aggregates with anle138b delays disease progression in a mouse model of tauopathies; Acta Neuropathol., 130 619
4) Martinez Hernandez et al. (2018), The diphenylpyrazole compound anle138b blocks Aβ channels and rescues disease phenotypes in a mouse model for amyloid pathology; EMBO Mol. Med., 10 32
5) Heras-Garvin et al. (2019), Anle138b modulates α-synuclein oligomerization and prevents motor decline and neurodegeneration in a mouse model of multiple system atrophy; Mov. Disord., 34 255
6) Brendel et al. (2019), Late-stage Anle138b treatment ameliorates tau pathology and metabolic decline in a mouse model of human Alzheimer’s disease tau; Alzheimer’s Res. Ther., 11 67
7) Turriani et al. (2017), Treatment with diphenyl-pyrazole compound anle138b reveals that α-synuclein protects melanoma cells from autophagic cell death; Proc. Natl. Acad. Sci. USA, 114 E4971