PolyQ aggregation inhibitor C2-8

C2-8 is an inhibitor of polyglutamine (polyQ) aggregation (IC50s=25 and 0.05 μM for recombinant HDQ51 and in PC12 cells, respectively). It also inhibits polyQ aggregation in organotypic hippocampal slice cultures isolated from R6/2 transgenic mice and reduces neurodegeneration in a dose-dependent manner in a Drosophila model of Huntington's disease. C2-8 (100 and 200 mg/kg) reduces huntingtin aggregate size, reduces neuronal atrophy, and improves motor performance in a rotarod test in the R6/2 transgenic mouse model of Huntington's disease.

[1]Zhang, et al. A potent small molecule inhibits polyglutamine aggregation in Huntington’s disease neurons and suppresses neurodegeneration in vivo. Proc. Natl. Acad. Sci. USA 102(3), 892-897 (2005).