TABLE 4

Effects of enzyme inhibition on the formation of MRX445-1, MRX445-2, and MRX459 from MRX-I (10 μM) in human liver S9 fractions

Protein concentration is 2.5 mg/ml.

Inhibitor or Process	Inhibitor Concentration	Target Enzyme	Metabolite Formation
Inhibitor or Process	Inhibitor Concentration	Target Enzyme	MRX445-1	MRX445-2	MRX459
	μM		%
No inhibitor (control)			100	100	100
ABT^{^a}	1000	P450s	91.2	91.6	88.7
Methimazole^{^a}	100	P450s, FMO1–FMO4	92.0	94.8	97.8
Heated^{^a}	—	FMO1, FMO3, FMO4, and FMO5	7.22	90.0	n.d.
Menadione^{^a}	10	AO and SDR	44.6	42.9	107
Raloxifene^{^a}	10	AO	83.1	19.9	98.0
Methotrexate^{^a}	50	XO	90.2	88.3	106
Allopurinol^{^a}	100	XO	110	103	94.2
Flufenamic acid^{^a}	100	AKR	69.4	75.2	88.1
4-MP^{^b}	100	ADH	103	88.5	93.3
Disulfiram^{^c}	50	ALDH	80.0	57.1	10.7