PIM Kinases as Potential Therapeutic Targets in a Subset of Peripheral T Cell Lymphoma Cases
Figure 8
Comparison between the compound ETP-39010 and other pan-PIMi.
(A) Selectivity profile showing the IC50 values of each of the compounds for the kinase activity of the indicated enzymes. (B) Percentage of inhibition of a panel of unrelated kinases by ETP-39010 and ETP-47551. A similar profile was found for ETP-47551, ETP-47652 and ETP-46638 compounds. (C) Sensitivity of PTCL cell lines to all pan-PIMi. (D) The newly developed pan-PIMi ETP-47551 reduced cell viability in all studied PTCL cell lines (IC50 values calculated after 72 h of treatment are shown). (E) The pan-PIMi ETP-47551 strongly induced apoptosis in a time-dependent manner in all studied PTCL cell lines (*, p<0.05, from comparison with DMSO-treated cells). The percentage of non-viable cells was calculated as Annexin V+/7AAD− plus Annexin V+/7AAD+ cells in the PIMi-treated condition minus the DMSO-treated control. (F) The combination of ALKi + ETP-39010 was highly synergistic only in ALK+ ALCL cell lines, as was (G) the combination of ALKi + ETP-47551 (Combination Index, CI, <1 indicates synergism between the two drugs; CI ≈1 indicates an additive effect; CI>1 indicates antagonism).