Figure 1

High-throughput screening of a FDA approved drug library identifies a class of antihelminthic benzimidazoles compounds that potentiate the effect of navitoclax in NSCLC cell lines. (A) Schematic representation of high-throughput FDA approved compound library screen. (B) Hcc827 cells were treated with the FDA approved drug library (640 compounds) in the presence or absence of 1 μM navitoclax. Four dilutions per compound (0.78, 3.13, 12.5, and 50 μM) were tested. Of the 40 compounds from the initial screen, 26 were validated and a class of antihelminthic benzimidazoles was chosen for further studies. Potentiation of navitoclax activity was calculated by % of cells remaining in the presence of these compounds plus navitoclax vs.% of cells remaining in the presence of these compounds alone. Validating anti-helminthic benzimidazoles potentiate navitoclax effect in three NSCLC cell lines. (C) Hcc827, (D) H292, and (E) H1993 cells were treated with increasing concentrations of albendazole or mebendazole in the presence of navitoclax (0, 1, 2, and 4 μM). Viability was determined after 1 day. Data shown are representative of at least two independent experiments.