Table 2.
In vitro inhibition of human drug metabolizing enzymes and transport proteins by entrectinib and M5
| IC50 (µM) | |||
|---|---|---|---|
| Entrectinib | M5 | ||
|
Drug Metabolizing Enzymes |
CYP1A2 | > 10 | > 10 |
| CYP2B6 | > 10 | > 10 | |
| CYP2C8 | > 10 | 4.9 | |
| CYP2C9 | > 10 | > 10 | |
| CYP2C19 | > 10 | > 10 | |
| CYP2D6 | > 10 | > 10 | |
| CYP3A4/5 | 2.0 | > 10 | |
| Transport Proteins | MDR1 (P-gp) | 1.3 | 10 |
CYP cytochrome P450, MDR multidrug resistance, P-gp P-glycoprotein
Entrectinib was a very weak time-dependent inhibitor (TDI) of CYP3A4 but KI and kinact could not be measured in vitro as the TDI signal was too low