Effect of PSMB5 mutations on growth inhibitory effects of bortezomib and epoxyketone-based proteasome inhibitors
Data presented are the mean of three to six separate experiments ± S.D. after 72-h drug exposure. Values in parentheses depict resistance factor [ratio IC50 selected cell line over parental (WT) cell line].
| Cell Line | PSMB5 Mutation, Amino Acid Shift | Bortezomib IC50 | Carfilzomib IC50 | ONX0912 IC50 | ONX0914 IC50 |
|---|---|---|---|---|---|
| nM | |||||
| THP1/WT | None | 3.5 ± 0.7 (1) | 16.4 ± 3.9 (1) | 69 ± 9 (1) | 99 ± 11 (1) |
| THP1/BTZ50 | Ala49Thr | 218 ± 39 (54) | 160 ± 4 (9) | 2686 ± 318 (39) | 2741 ± 428 (27) |
| THP1/BTZ500 | Ala49Thr and Met45lle | 823 ± 65 (235) | 501 ± 69 (32) | 4395 ± 458 (62) | 10,092 ± 1642 (97) |