Figure 2
From: A cellular screen identifies ponatinib and pazopanib as inhibitors of necroptosis
Ponatinib and pazopanib efficiently and specifically block necroptosis. (a and b) Cell viability was determined in FADD-deficient Jurkat cells treated overnight with (red circles) or without (blue rectangles) 10 ng/ml TNF-α and drugs as indicated. (c) Cell viability was assessed in HT-29 cells treated overnight with 20 ng/ml TNF-α (T), 500 nM Smac mimetic (S), 20 μM caspase inhibitor z-VAD (Z) and the compounds indicated (Nec-1, 10 μM; all others, 1 μM). (d) HT-29 cells were treated with TSZ and ponatinib or pazopanib as indicated. (e) HT-29 cells were treated with ponatinib or pazopanib at concentrations indicated for 24 h. (f) Cell viability was assessed in HT-29 cells treated overnight with 200 ng/ml TRAIL or (g) 200 ng/ml human FasL together with 500 nM Smac mimetic (S), 20 μM z-VAD (Z) and either 10 μM Nec-1, 0.5 μM ponatinib or 5 μM pazopanib. Data represent mean value±S.D. of two independent experiments performed in triplicates and normalized to untreated control. (h) Cell viability was determined in Jurkat E6.1 cells treated with 100 ng/ml human FasL and 10 μM z-VAD, 10 μM Nec-1, 0.5 μM ponatinib or 5 μM pazopanib for 24 h. 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
