TABLE 1.
Summary of IC50 values for inhibition of uridine transport in yeast and CEM cells
Inhibition of [3H]uridine uptake by BCR-ABL TKIs was assessed in yeast producing each of the five recombinant hNTs and in CEM cells, which have only hENT1 activity, in concentration-effect experiments as described under “Experimental Procedures.” IC50 values (mean ± S.E.) are listed below.
| Transporter yeast | IC50 |
||||
|---|---|---|---|---|---|
| Bosutinib | Dasatinib | Imatinib | Nilotinib | Ponatinib | |
| μm ± S.E. | |||||
| hENT1 | 13.0 ± 1.0 | 60.0 ± 3.0 | 110.0 ± 26.0 | 0.7 ± 0.1 | 9.0 ± 0.1 |
| hENT2 | 24.0 ± 2.0 | 240.0 ± 57.0 | 230.0 ± 11.0 | 150.0 ± 21.0 | 33.0 ± 1.0 |
| hCNT1 | 260.0 ± 6.0 | 84.0 ± 1.0 | 130.0 ± 5.3 | >300 | 22.0 ± 3.0 |
| hCNT2 | >300 | >300 | 2.3 ± 0.3 | >300 | 64.0 ± 6.0 |
| hCNT3 | 150.0 ± 3.0 | 170.0 ± 20.0 | 62.0 ± 2.0 | >300 | 70.0 ± 3.0 |
| CEM | 2.0 ± 0.4 | 8.0 ± 1.6 | 16.0 ± 2.0 | 0.7 ± 0.01 | 3.0 ± 0.2 |