Figure 1.

Discovery of statins as Nurr1 modulators and their profiling. a) Primary fragment screening results. Nurr1 modulatory activity of the entire drug fragment library in a Gal4‐Nurr1 hybrid reporter gene assay. Data are the mean reporter activity versus 0.4% DMSO at 100 × 10⁻⁶ m; n = 2. Different colors represent different graph frameworks (see also Figure S1, Supporting Information). Compounds marked with a star relate to the fragment hits validated in control experiments on Gal4‐VP16. Gray lines represent mean ± SD of the entire screening. b) Nurr1 modulatory activity of the fragment screening hit and of the statin class of drugs (vs 0.1% DMSO) in a Gal4‐Nurr1 hybrid reporter gene assay. Data for chloroquine (CQ) from ref. [15]. Data are the mean ± S.E.M.; n ≥ 3. c) Multiple alignment of fluvastatin (FLU), pitavastatin (PITA), and amodiaquine (AQ) reveals common structural features with overlap of the indole and quinoline scaffolds as well as the phenyl substituents.