TABLE 4

Use of 50 μM hydralazine, a specific AO inhibitor, to determine the fm,AO in human hepatocytes

AO StatusCompoundMean Hepatocyte t1/2 ± S.E.a
­–Hydralazinea+Hydralazinefm,AO
minmina%
SubstrateA77-0110 ± 0.125 ± 260
Bafetinib22 ± 253 ± 0.458
Carbazeran9 ± 0.181 ± 389
CL-38778516 ± 430 ± 747
Duvalisib185 ± 7294 ± 2537
Imatinib208 ± 16246 ± 3BQL (15)b
INCB28060115 ± 0.8154 ± 4BQL (25)b
Lapatinib130 ± 11132 ± 7BQL (2)b
Lapatinib M150 ± 168 ± 0.5BQL (26)b
LDN-19318927 ± 2119 ± 977
ML-34736 ± 0.0757 ± 237
SB-52534442 ± 0.07>700>94
VX-509132 ± 14127 ± 2BQL (-4)b
Zoniporide58 ± 0.9>700>92
NonsubstrateCeritinib362 ± 5268 ± 12BQL (–35)b
GDC-0068103 ± 3115 ± 1BQL (11)b
KIRA651 ± 1049 ± 1BQL (–4)b
Linsitinib54 ± 474 ± 2BQL (28)b
Midazolam39 ± 142 ± 0.3BQL (7)b
Neratinib51 ± 0.258 ± 8BQL (13)b
Oclacitinib416 ± 13414 ± 16BQL (0)b
OSI-027810 ± 2081098 ± 322BQL (26)b
OXA-01613 ± 30887 ± 33BQL (31)b
SGI-1776139 ± 0.02156 ± 7BQL (11)b
THZ185 ± 1193 ± 8BQL (8)b
Vatalanib48 ± 0.849 ± 0.2BQL (3)b
  • BQL, below the quantitation limit (33% in this assay).

  • a n = 2.

  • b Results of fm,AO calculation in parentheses.