Inhibitors and recommended concentration range for non-P450 enzymes to use in vitro phenotyping studies
| Enzyme | Selective Substrates (Km) | Selective Inhibitor | Recommended Inhibitor Concentration Range (reported IC50 value) | References |
|---|---|---|---|---|
| µM | µM | |||
| AO | DACAa (8) | Hydralazine | 0.05–50 (IC50 = 0.5–5b) | Johnsonet al., 1985; |
| Phthalazine (5) | Raloxifenec | 0.0001–1 (IC50= 0.0029) | Chen et al., 2002; | |
| Menadionec | 0.01–100 (IC50= 0.2) | Obach, 2004; | ||
| Strelevitz et al., 2012; | ||||
| Barr and Jones, 2011, 2013 | ||||
| XO | Pterin (34) | Allopurinol | 0.01–100 (IC50= 2) | Obach, 2004; Panoutsopoulos et al., 2004; Tapner et al., 2004; Pacher et al., 2006 |
| 6-mercaptopurine(6) | ||||
| MAO-A | Serotonin(100) | Clorgyllined * | 0.0002–2 (IC50= 0.002) | Leonardi and Azmitia, 1994; Kalgutkar and Castagnoli, 1995; Herraiz, 2009, 2012; Geha et al., 2001 |
| MAO-B | β –phenylethylamine(2) | (-) Deprenyld * | 0.0002–2 (IC50= 0.001) | Geha et al., 2001; Herraiz, 2009, 2012; |
| FMO (1, 3, and 5) | Benzydamine (FMO 1 = 24; FMO3 = 40) | Methimazole | 10–500 (IC50= 120) | Störmer et al.,2000 |
↵a DACA = N-[(2-dimethylamino)ethyl]acridine-4-carboxamide.
↵b Demonstrates substrate-dependent IC50.
↵c Suitable in liver cytosol, but less suitable for inhibition studies in liver S9 fractions or hepatocytes because of their potential to inhibit P450 enzymes and/or instability.
↵d Pargylline can also be used as non-specific inhibitor of MAO (Recommended concentration for phenotyping studies 0.5–2 µM; IC50 for MAO-A is 0.01152 µM and for MAO-B is 0.00820 µM) (Fisar et al., 2010; Murphy et al., 1998).
↵* Irreversible inhibitors