Fig. 3
In vivo analysis of inhibitor 1 and its derivatives. a Representative pseudopupil images from 7 day old wild-type control flies and HD flies (treated with either vehicle (DMSO) or 10 μM/100 μM inhibitor 1). Control flies exhibit seven visible rhabdomeres per ommatidium, whereas degeneration of these photoreceptor neurons is observed in HD flies. b Rhabdomere quantification of HTT93Q flies treated with inhibitor 1. Newly enclosed HTT93Q flies were treated with 10 μM or 100 μM inhibitor 1 for 7 days. n = 11–14 flies per condition as labelled in the figure. *P < 0.05, **P < 0.01, ****P < 0.0001, ANOVA with Newman–Keuls post hoc test. Untreated and DMSO-treated groups served as controls. c The concentration of inhibitor 1 detected in the brain at 5 min and 60 min after a single intravenous administration in the mouse. The concentration of inhibitor 1 in the blood was plotted as ng/mL and in the brain was plotted as ng/g. The number above each column is the mean brain:blood ratio of inhibitor 1 detected in the sample, NR = no result as concentration below limit of detection (n = 3 mice, **P < 0.01, ANOVA with Tukey post hoc test). d The effect of inhibitor 1 and prodrugs on the fluorescence of K562 cells incubated with riboflavin (or without as a control) and read over 300 s (n = 300). e The concentration of inhibitor 1 detected in the brain and blood after single intravenous administration of prodrug 1b in the rat (n = 3 rats). The number above each column is the mean brain:blood ratio of inhibitor 1 detected in the sample. f Percentage of [5-3H]-KYN that is metabolised into [3H]-3-HK in the striatum of awake rats 1 h after an intravenous injection of vehicle, prodrug 1b, or Ro 61-8048. n = 6–10 rats as indicated in the figure panel, **P < 0.01, one-way ANOVA with Bonferroni’s multiple comparisons post hoc test. In panels c through e the values are expressed as the mean ± SEM
