(3Z)-5-bromo-3-[(3-bromo-4,5-dihydroxyphenyl)methylidene]-1H-indol-2-one

Uses

LC3-mHTT-IN-AN1 (Compound AN1) is a mHTT-LC3 linker compound, which interacts with both mutant huntingtin protein (mHTT) and LC3B but not with wtHTT or irrelevant control proteins. LC3-mHTT-IN-AN1 reduces the levels of mHTT in an allele-selective manner in cultured Huntington disease (HD) mouse neurons[1].

Biological Activity

AN1 is a brain blood barrier penetrant agent th at tether LC3 and mHTT and targets mHTT for autophagosome degradation. AN1 significantly lower mHTT in cortices of HD mice, in cells from patients with Huntington′s disease, and neurons derived from induced pluripotent stem cells. AN1 does not lower wtHTT in fibroblasts from healthy human donors. It appears th at AN1 interact with the polyQ stretch.

References

[1] Li Z, et al. Allele-selective lowering of mutant HTT protein by HTT-LC3 linker compounds. Nature. 2019 Nov;575(7781):203-209. DOI:10.1038/s41586-019-1722-1