Figure 3.

(A) Screening of a library of approved protein kinase inhibitors for inhibition of human CD39 (expressed in umbilical cord membranes) using the malachite green assay. A concentration of 10 µM of the test compounds was employed. Data points represent means±SEM of three separate experiments. Hit compounds: ceritinib, p value <0.0001; ponatinib, p value <0.0478. The data were analyzed by one-way analysis of variance and Dunnett’s multiple comparison test towards the normalized control without the inhibitors. (B) Structures of approved protein kinase inhibitors identified in a screening approach to significantly block the ectonucleotidase CD39. Ceritinib, a potent anaplastic lymphoma kinase (ALK) inhibitor approved for ALK-positive metastatic non-small cell lung cancer in patients with inadequate clinical response or intolerance to crizotinib,75 and ponatinib, a multitarget tyrosine kinase inhibitor used for the treatment of chronic myeloid leukemia and Philadelphia chromosome–positive acute lymphoblastic leukemia.76