Table 5. In vitro inhibition assays of 18 tested compounds.
| Drug name | Cluster | Inhibition of CYP2C9 activity in HepG2 cells* (yes/no) |
Dose- dependent inhibition (yes/no) |
Increased cytotoxicity in HepG2 cells expressing CYP2C9 (min [c]; % living cells)** |
IC50 values determined with CYP2C9 supersomes (μM) |
|---|---|---|---|---|---|
| Abemaciclib | 1 | no | no | yes (5μM; 30%) | >100 |
| Mizolastine | 2 | no | no | yes (50 μM; 60%) | |
| Sertindole | 3 | yes | yes | yes (10 μM; 60%) | 40 |
| Cloperidone | 3 | yes | yes | yes (100 μM; 40%) | 17.7 |
| Sivelestat | 5 | no | no | no | |
| Asapiprant | 6 | yes | yes | no | 46 |
| Pf-562271 | 7 | yes | no | yes (10 μM; 65%) | |
| Ciltoprazine | 8 | yes | no | yes (75 μM; 0%)*** | |
| Vatalanib | 10 | yes | yes | yes (20 μM; 50%) | 0.067 |
| Entinostat | 11 | no | no | no | |
| Azd3514 | 12 | no | no | yes (20 μM; 60%) | |
| Muraglitazar | 14 | no | no | no | |
| Bifeprofen | 16 | yes | yes | yes (75 μM; 50%) | |
| Tarafenacin | 22 | yes | no | yes (50 μM; 0%) | >100 |
| Ticagrelor | 23 | yes | yes | no | 11.8 |
| Duvelisib | 24 | yes | yes | no | 52 |
| Dasatinib | 24 | yes | yes | yes (20 μM; 45%) | 85 |
| Piriqualone | 24 | yes | yes | yes (75 μM; 0%)*** | 10.9 |
* For each compound, the inhibition tests were performed over a range of concentrations selected such that the highest concentration yielded a cell viability (based on MTS assay) greater than 80%.
** min [c]: minimal concentrations that increase the cytotoxicity (> threshold fixed at a cell viability of 80%) and percentage (%) of living HepG2 cells expressing CYP2C9 after incubation with the “min [c]” of the compound. At the same concentration, no cytotoxic effect (% living cells > 80%) was observed in the wild-type HepG2 cells incubated with the compound.
*** For ciltoprazine and piriqualone, the cytotoxicity was also observed in wt HepG2 cells at high concentrations, but the % of living cells with all concentrations (including 100 μM) was maintained at > 50%.