TABLE 3

Median induction parameters EC50 (μM) and Emax from mRNA levels after treatment with CD 6168 in three human hepatocyte donors

P450 IsoformCD 6168 or Deleobuvir-AGaPrototypical Inducerc
EC50 (μM)Emax FoldEmax/EC50EC50 (μM)Emax FoldEmax/EC50
TotalFreeb
CYP1A2a6.20.716.79.411.920.41.7
CYP2B61.10.183.82159510.20.017
CYP2C82.70.435.914NC5.1NC
CYP2C90.250.0402.153NC2.5NC
CYP3A40.390.05812.42140.81326.833
  • NC, not calculable, the dynamic range was insufficient to generate non-ambiguous fitting parameters therefore the Emax reported is the maximal fold change observed over the rifampicin incubation concentrations.

  • a CYP1A2 induction parameters are from deleobuvir-AG incubations; for other isoforms parameters are from CD 6168 incubations.

  • b Adjusted for protein binding in induction media which contains bovine serum albumin in the insulin, transferrin and selenium ITS supplement.

  • c Prototypical inducers were omeprazole (CYP1A2), phenobarbital (CYP2B6), and rifampicin (CYP2C8, CYP2C9, and CYP3A4).