TABLE 1

Substrate depletion results for the metabolism of 43 drugs by six BM3 mutants

Compound	M01	M02	M11	MT35	MT38	MT43	HLMs
	500 pmol/ml^{^a}						1 mg/ml^{^a}
Alprazolam	<5^{^b}	<5^{^b}	<5^{^b}	10	<5^{^b}	<5^{^b}	<5^{^b}
Amitriptyline	36	34	74	96	84	25	18
Aprepitant	10	<5^{^b}	10	<5^{^b}	9	17	45
Aripiprazole	99	99	99	93	99	99	93
Astemizole	95	8	94	68	<5^{^b}	10	22
Buspirone	46	75	83	67	9	29	17
Carbamazepine	<5^{^b}	<5^{^b}	<5^{^c}	11	<5^{^b}	10	<5^{^b}
Carvedilol	86	9	78	66	51	32	8
Cilostazol	<5^{^b}	25	17	37	82	93	38
Cinacalcet	96	89	97	87	67	96	46
Citalopram	29	7	56	78	27	10	<5^{^b}
Dextromethorphan	68	23	95	97	80	50	27
Diclofenac	18	<5^{^b}	13	50	<5^{^b}	7	45
Diltiazem	6	<5^{^b}	<5^{^b}	55	11	10	28
Duloxetine	18	<5^{^b}	39	51	53	20	<5^{^b}
Glipizide	<5^{^b}	<5^{^b}	7	35	<5^{^b}	9	44
Imatinib	51	80	77	30	13	<5^{^b}	<5^{^b}
Indomethacin	<5^{^c}	<5^{^c}	<5^{^c}	<5^{^c}	<5^{^c}	<5^{^c}	<5^{^b}
Irbesartan	12	<5^{^b}	7	80	23	6	<5^{^b}
Lacosamide	<5^{^b}	<5^{^b}	<5^{^b}	<5^{^b}	7	<5^{^b}	<5^{^b}
Meloxicam	<5^{^c}	<5^{^c}	<5^{^c}	<5^{^c}	<5^{^c}	<5^{^c}	<5^{^b}
Midazolam	<5^{^c}	<5^{^c}	<5^{^c}	40	<5^{^c}	<5^{^c}	36
Minaprine	11	6	<5^{^b}	19	7	9	<5^{^b}
Nelfinavir	7	<5^{^b}	<5^{^b}	<5^{^b}	24	37	<5^{^b}
Nicotine	36	8	<5^{^b}	43	37	21	48
Nifedipine	63	32	<5^{^b}	<5^{^b}	58	67	<5^{^b}
Nilotinib	9	23	<5^{^b}	21	10	10	24
Ondansetron	30	6	11	9	18	30	6
Paroxetine	10	6	41	17	17	6	<5^{^b}
Phenacetine	<5^{^b}	<5^{^b}	<5^{^b}	<5^{^b}	<5^{^b}	6	9
Pimozide	16	38	<5^{^b}	26	37	11	<5^{^b}
Propafenone	10	<5^{^b}	21	23	22	21	<5^{^b}
Quinidine	<5^{^b}	17	9	23	<5^{^b}	<5^{^b}	<5^{^b}
Repaglinide	<5^{^b}	<5^{^b}	13	55	<5^{^b}	<5^{^b}	33
Rosiglitazone	99	99	95	82	76	99	<5^{^b}
R-warfarin	6	<5^{^b}	<5^{^b}	<5^{^b}	<5^{^b}	<5^{^b}	<5^{^b}
Saquinavir	<5^{^b}	<5^{^b}	<5^{^b}	35	<5^{^b}	8	52
Sorafenib	<5^{^c}	<5^{^b}	36	<5^{^b}	38	36	71
Tamoxifen	62	68	36	28	63	73	8
Terfenadine	10	21	7	7	62	54	<5^{^b}
Thioridazine	99	91	96	97	97	83	7
Tipranavir	23	<5^{^c}	<5^{^b}	63	63	69	58
Verapamil	<5^{^b}	<5^{^b}	<5^{^b}	27	<5^{^b}	<5^{^b}	30

a The substrate depletion is calculated by using the average peak area of the parent at 90 min and at time zero. Values are expressed in percentages of the average peak area of the parent at time zero. Measurements were performed in duplicate.
b The calculated substrate depletion was below the overall precision (CV) of the screening assay but minor amounts of P450-mediated metabolites were detected by LC-MS.
c The calculated substrate depletion was below the overall precision (CV) of the screening assay and no P450-mediated metabolites could be detected by LC-MS.