Table 4

K11777 metabolite formation rates by human cDNA-expressed CYP enzymes and cDNA-expressed FMO3.

Enzyme	N-Oxide K11777		β-Hydroxy-homoPhe K11777		N-Desmethyl K11777
	pmol/pmol CYP · min [pmol/mg protein · min]
1A1	0.091 ± 0.009	[12.8 ± 1.2]	0.015 ± 0.002	[2.0 ± 0.3]	0.145 ± 0.017	[20.5 ± 2.4]
1A2	0.079 ± 0.002	[21.0 ± 0.6]	0.028 ± 0.001	[7.3 ± 0.3]	0.153 ± 0.002	[40.3 ± 0.7]
2B6	0.046 ± 0.001	[5.9 ± 0.2]	<LOD		0.070 ± 0.005	[9.0 ± 0.6]
2C8	0.164 ± 0.006	[82.0 ± 2.8]	0.038 ± 0.003	[18.8 ± 1.4]	0.192 ± 0.006	[95.7 ± 3.0]
2C9-Arg	0.044 ± 0.002	[21.1 ± 1.0]	<LOD		0.047 ± 0.003	[22.7 ± 1.3]
2C19	0.057 ± 0.005	[20.5 ± 1.8]	<LOD		0.046 ± 0.001	[16.6 ± 0.1]
2D6	0.168 ± 0.014	[27.5 ± 2.3]	<LOD		4.37 ± 10.6	[717 ± 58.3]
2E1	0.023 ± 0.001	[13.4 ± 0.5]	<LOD		<LOD
3A4	0.877 ± 0.105	[87.0 ± 10.4]	0.320 ± 0.047	[31.7 ± 4.7]	0.550 ± 0.037	[54.7 ± 3.7]
3A5	0.166 ± 0.003	[124 ± 2.1]	0.024 ± 0.001	[17.8 ± 0.4]	0.124 ± 0.001	[93.0 ± 0.6]
FMO
FMO3		[1800 ± 97.7]	<LOD		<LOD

K11777 (final concentration: 100 μM) was incubated for 15 min with 25 pmol of CYP enzymes isolated from baculovirus-infected insect cells expressing human CYP 1A1, 1A2, 2B6, 2C8, 2C9-Arg, 2C19, 2D6, 2E1, 3A4, or 3A5 and 0.125 mg of microsomal protein isolated from baculovirus-infecting insect cells expressing human FMO3.

LOD, concentration below lower limit of detection (0.5 ng/ml).