Time-dependent inhibition results for GalNAc siRNAs against P450s
| P450 Isoform | IC50 (µM) | ||||||||
|---|---|---|---|---|---|---|---|---|---|
| Inclisiran | AGT01 | HBV02 | |||||||
| −NADPH | +NADPH | Ratio | −NADPH | +NADPH | Ratio | −NADPH | +NADPH | Ratio | |
| CYP1A2 | >612 | >612 | 1 | >18.3 | >18.3 | 1 | >20 | >20 | 1 |
| CYP2B6 | >612 | >612 | 1 | >18.3 | >18.3 | 1 | >20 | >20 | 1 |
| CYP2C8 | >612 | >612 | 1 | >18.3 | >18.3 | 1 | >20 | >20 | 1 |
| CYP2C9 | >612 | >612 | 1 | >18.3 | >18.3 | 1 | >20 | >20 | 1 |
| CYP2C19 | >612 | >612 | 1 | >18.3 | >18.3 | 1 | >20 | >20 | 1 |
| CYP2D6 | >612 | >612 | 1 | >18.3 | >18.3 | 1 | >20 | >20 | 1 |
| CYP3A4/5 (midazolam) | >612 | >612 | 1 | >18.3 | >18.3 | 1 | >20 | >20 | 1 |
| CYP3A4/5 (testosterone) | >612 | >612 | 1 | >18.3 | >18.3 | 1 | >20 | >20 | 1 |