Fig. 4

Drug screening identifies fimepinostat as an effective treatment for small cell lung cancer in vitro. A Platinum resistant mouse SCLC cell line EN84R was screened for sensitivity to 355 kinase inhibitors at 100 nM for 7 days and the average viability z-score of three independent experiments plotted. Drugs achieving a Z-score of -3 > z > -2 are shown in blue and drugs where z < -3 are shown in red. Fimepinostat is highlighted. B Drug screening was performed in triplicate on the indicated cell lines and a heat map of average Z scores for the top 10 hits shown in all cell lines. C Dose response curves for fimepinostat sensitivity in a panel of human SCLC cell lines and PDX lines. Data represents the % viability at indicated dose (Log₂ nM) and LD₅₀ (nM) calculated using Prism. D Fimepinostat LD₅₀ (nM) doses determined for matched platinum naïve and resistant mouse SCLC cell lines and primary (1°) mouse lung epithelium. Statistically significant differences in viability between 1° epithelium and SCLC cell lines were determined by 2-way ANOVA (*p < 0.05, **p < 0.005, ***p < 0.001, ****p < 0.0001)