TABLE 8

In vitro conversion of semagacestat to M3, incubated at 1, 10, or 500 μM, by a panel of recombinant human P450 enzymes

Test System^a	M3 Formation
Test System^a	1 μM Semagacestat	10 μM Semagacestat	500 μM Semagacestat
	pmol/min/pmol P450	pmol/min/pmol P450	pmol/min/pmol P450
Control Bactosomes	N.D.	N.D.	N.D.
Reductase control	N.D.	N.D.	N.D.
Insect cell control + b5	N.D.	N.D.	N.D.
CYP1A2	N.D.	N.D.	N.D.
CYP2B6	N.D.	N.D.	N.D.
CYP2C8 + b5	0.002	0.014	0.475
CYP2C9 + b5	N.D.	0.000	0.015
CYP2C19 + b5	N.D.	0.005	0.159
CYP2D6	N.D.	0.003	0.097
CYP3A4 + b5	0.016	0.179	3.900^b
CYP3A5 + b5	0.030	0.251	4.173^b

N.D., not detected.
↵a + b5, coexpressed with cytochrome b5.
↵b Values listed were above the quantitation limit; thus, they are shown for qualitative purposes only.