Table 1.
Growth-inhibitory effects of PI3-kinase (PI3K) inhibitors and BCR-ABL1-targeting drugs on endothelial cells, osteoblasts, monocytic cells and CML cell lines
| Cell line | IC50 (μM) Nilotinib | IC50 (μM) Ponatinib | IC50 (μM) Imatinib | IC50 (μM) Asciminib | IC50 (μM) BEZ235 | IC50 (μM) Copanlisib | IC50 (μM) Rapamycin |
|---|---|---|---|---|---|---|---|
| HMEC-1 | 0.1-0.5 | 0.1-0.5 | >10 | >5 | 0.5-1 | 0.5-1 | 3-5 |
| HUVEC | 0.5-1 | 0.1-0.5 | >10 | 2.5-5 | 0.05-0.5 | 0.05-0.5 | 0.5-1 |
| CAL-72 | 0.1-0.5 | 0.1-0.5 | 2.5-5 | >5 | 0.1-0.5 | 0.5-1 | 0.5-1 |
| Primary osteoblasts | 0.01-0.05 | 0.5-1 | 5-10 | >5 | 0.01-0.05 | 0.05-05 | 0.5-1 |
| THP-1 | 1-2 | 0.5-1 | >10 | >5 | 0.1-0.5 | 0.05-0.5 | >5 |
| Mono Mac 6 | 0.5-1 | 0.01-0.05 | >10 | >5 | 0.1-0.5 | 0.05-0.5 | 2-3 |
| KU812 | 0.01-0.015 | 0.00005-0.001 | 0.25-0.3 | 0.0025-0.005 | 0.05-0.5 | 0.05-0.5 | 3-5 |
| K562 | 0.015-0.02 | 0.0001-0.0005 | 0.4-0.5 | 0.02-0.05 | 0.05-0.5 | 0.5-1 | 3-5 |
Niche cells and CML cell lines were incubated in various concentrations of BEZ235, rapamycin, nilotinib, ponatinib, imatinib, asciminib or copanlisib at 37°C for 48 hours. Then, proliferation was measured by determining 3H-thymidine uptake. The table provides the IC50 values (ranges) obtained from at least three independent experiments. Abbreviations: BCR-ABL1; break point cluster region-Abelson murine leukemia viral oncogene homolog1; CML, chronic myeloid leukemia; IC50, half maximal inhibitory concentration; HMEC-1, human microvascular endothelial cell; HUVEC, human umbilical vein endothelial cell.