Large-Scale Analysis of Cancer Cell Fractional Killing

In the clinic, few drugs are employed as single agents and it is therefore of interest to understand the impact of drug interactions specifically on fractional killing. Our ability to monitor fractional killing in many populations in parallel provided a means to search for modulators of this phenomenon more systematically. As proof-of-principle, we examined the effect on pimasertib (Pim, 5 µM)-induced cell death of 261 structurally and functionally distinct compounds in A549^N cells. The ability of all 261 compounds to modulate Pim-induced cell death was computed using an analytic framework based on the Bliss model of drug interactions.

The files below contain the raw live (mKate2 positive), dead (SYTOX Green positive) and overlapping (mKate2 positive/SYTOX Green double positive; treated as dead cells in the computation of lethal fraction scores) counts, along with the computed lethal fraction scores, for each compound. Library wells denoted as 'Empty' contained DMSO and function as controls in the DMSO treatment or pimasertib treatment conditions.

Note that each screen was repeated three independent times (reps 1,2,3). Time elapsed is in hours.