TABLE 3

Summary of kinetic parameters from Michaelis-Menten analysis of epoxide hydrolysis of KZR-616 (data represent mean ± S.D.; duplicate incubations; efficiency defined as Vmax/Km).

Epoxide HydrolysisKinetics of the Formation of KZR-59587 from In Vitro Enzymatic Assays
KmVmaxVmax/Km
μMnmol/min/mg protein% of mEH
Recombinant mEHa2172 ± 341555 ± 64.10.256 ± 0.029
Male HLM987 ± 33817.2 ± 3.480.017 ± 0.004 (6.82%)
Female HLM1862 ± 106524.2 ± 9.810.013 ± 0.0045 (5.07%)
Male MLM178 ± 25.931.1 ± 1.570.175 ± 0.009 (68.4%)
Female MLM191 ± 27.134.1 ± 1.720.179 ± 0.009 (69.9%)
Epoxide hydrolysisKinetics of the Formation of KZR-59587 from Cell-Based Assays
KmVmaxVmax/Km
μMpmol/min/106 cells% of hepatocytes
Human hepatocytesb76.7 ± 20.14674 ± 32560.9 ± 4.23
  • aRecombinant mEH used as control value for comparing the percentage efficiency among enzymatic assays.

  • bHuman hepatocytes used as control value for comparing the percentage efficiency among cell-based assays.