Table 1.

CYP- and FMO-dependent catalytic activities and amounts of cabozantinib metabolites in samples of human liver microsomes.

	Total CYPs a	POR b	Cyt b5 c	CYP1A2 d	CYP2A6 d	CYP2B6 d	CYP2C8 d	CYP2C9 d	CYP2C19 d	CYP2D6 d	CYP2E1 d	CYP3A4 d	CYP4A11 d	FMO d	M1 e	M2 e	M3 e
HG03	290	450	380	170	2000	51	200	1700	44	110	1800	6100	1600		0.287	0.335	1.672
HG103	340	210	790	310	440	7.2	39	2300	23	65	1100	2200	1600	1400	0.109	0.144	0.644
HG24	260	260	550	1700	1500	35	190	3000	41	-	2300	4000	1800	1500	0.132	0.149	0.752
HG32	170	330	580	730	520	0.68	20	450	4.8	46	1200	2000	680	920	0.208	0.185	1.338
HG42	670	510	500	700	2200	150	480	1600	7.4	95	1600	15,000	1400	2000	0.301	0.329	1.609
HG43	270	210	640	580	770	14	25	1800	440	4	780	4600	1800	920	0.755	0.625	3.491
HG74	220	200	600	520	360	13	130	2100	55	120	1400	2700	1300	1200	0.148	0.256	1.106
HG93	430	320	450	691	350	43	270	2200	75	49	2800	2800	1800	3500	0.292	0.371	1.935
HK23	380	380	700	960	1100	24	160	2100	110	140	2100	6800	780	2500	0.094	0.130	0.607
HK27	300	450	730	1320	1320	31	180	480	460	130	3000	4910	1110	2230	0.273	0.467	2.228
HK31	580	540	770	1220	2160	8.1	130	1690	172	3.4	1660	8210	2010	3020	0.218	0.377	1.537
HK34	500	460	890	1000	1500	39	220	1900	45	100	6000	5200	1100	2700	0.209	0.305	1.359

^a Total CYP in pmol CYP/mg protein; ^b POR activity of cytochrome c reductase (pmol/mg protein); ^c Cyt b₅ was determined spectrophotometrically (pmol/mg protein); ^d CYP- and FMO-specific activity in pmol product/(mg protein × min): Phenacetin-O-deethylase (CYP1A2), Coumarine-7-hydroxylase (CYP2A6), (S)-Mephenytoin-N-demethylase (CYP2B6), Paclitaxel-6α-hydroxylase (CYP2C8), Diclofenac-4′-hydroxylase (CYP2C9), (S)-Mephenytoin-4′-hydroxylase (CYP2C19), Buferalol-1′-hydroxylase (CYP2D6), Chlorzoxazone-6-hydroxylase (CYP2E1), Testosterone-6β-hydroxylase (CYP3A4), Lauric acid-12-hydroxylase (CYP4A11), Methyl-p-tolyl sulfide oxidase (FMO); ^e Amounts of cabozantinib metabolites as peak area/incubation time.