Figure 1.

A cell-based drug screen identifies ponatinib and pazopanib as necroptosis inhibitors. (a) Schematic overview of the drug screen workflow. (b) Normalized necroptosis inhibition values depicted as percentage of control (DMSO=0, Nec-1 [10 μM]=100) for drugs tested on FADD-deficient Jurkat cells treated overnight with 10 ng/ml TNF-α. Values represent mean value±S.D. for 268 drugs assayed at 1.5 (dark gray) or 0.5 μM (light gray) in duplicates, respectively. (c) FADD-deficient Jurkat cells were treated overnight with 10 ng/ml TNF-α and ponatinib or pazopanib as indicated. Data were normalized to untreated control cells and represent mean value±S.D. of four independent experiments performed in triplicates. (d) FADD-deficient Jurkat cells were treated for 24 h with ponatinib or pazopanib as indicated. Data represent mean value±S.D. of two independent experiments performed in triplicates and normalized to untreated control. Cell viability was assessed using a luminescence-based readout for ATP (CellTiter Glo) throughout