Fig. 1. P300/CBP inhibitor A-485 was identified as a sensitizer to idelalisib by a combinatorial drug screen in MCL cells.

a Epigenetic compound libraries used for the screen. The numbers in parentheses indicate the numbers of compounds in each category used for the screen. b A schematic showing the approach used for the combinatorial drug screen. Z-138 cells were seeded in triplicate in 96-well plates and treated with increasing doses of each of the 45 candidates in the presence or absence of 2 μM idelalisib (idela). c Histogram showing the results of the idelalisib screen. Agents were ranked according to the largest difference in AUC between the two dose–response curves in Z-138 cells. d Chemical structure of the hit compound A-485. e Validation of the hit compound in MCL cells. A growth assay in Maver-1, Z-138, and Jeko-1 cells was performed following 96 h of exposure to the indicated agents at progressively increasing doses. f Combination index (CI) analysis. The survival fraction affected (Fa) and CI value are shown for Maver-1, Z-138, and Jeko-1 cells. The CI quantitatively determines synergy (CI < 1), an additive effect (CI = 1), or antagonism (CI > 1). The data shown are the mean ± SD of experiments completed in triplicate. At least three biological replicates were performed for all assays.