Inhibitor | Therapeutic Use and/or Drug Class | Mode of Inhibition | Preinc. IC50a | IC50 Shiftb | KI | kinact | Test System | Marker Reactionc | References |
---|---|---|---|---|---|---|---|---|---|
µM | ratio | µM | 1/min | ||||||
17α-Ethinylestradiol | Contraceptive, hormone derivative | 8.3 | 1.9 | HLM | Pacli | Chang et al., 2009 | |||
Amiodarone | Antiarrhythmic | 1.5 | 0.079 | rCYP2C8 | Pacli | Polasek et al., 2004 | |||
51.2 | 0.029 | HLM | Pacli | Polasek et al., 2004 | |||||
Bosutinib | Anticancer, PKI | 16.9 | 2.6 | 54.8 | 0.018 | HLM | Amo | Filppula et al., 2014 | |
Clopidogrel acyl 1-β-D-glucuronide | Drug metabolite | 12.0 | 4.7 | 9.9 | 0.047 | HLM | Amo | Tornio et al., 2014 | |
Desethylamiodarone | Drug metabolite | 0.67 | 3.3 | 4.4 | 0.009 | HLM | Amo | Obach et al., 2007 | |
Demethyldabrafenib | Drug metabolite | 30a | 1.6 | HLM | Rosi | Lawrence et al., 2014 | |||
Fluoxetine | Antidepressant, SSRI | Quasi-irreversible | 294 | 0.083 | rCYP2C8 | Pacli | Polasek et al., 2004 | ||
Gemfibrozil 1-O-β glucuronide | Drug metabolite | Irreversible | 1.8 | 13.3 | 20-52 | 0.21 | HLM | Pacli | Ogilvie et al., 2006 |
4.51 | 0.106 | Hep | n/a | Negishi et al., 2007 | |||||
29 | 0.072 | rCYP2C8 | Amo | Baer et al., 2009 | |||||
0.46 | 98 | HLM | Amo | Perloff et al., 2009 | |||||
3.0 | HLM | Monte | Karonen et al., 2010 | ||||||
4.5 | HLM | Monte-4 | Karonen et al., 2010 | ||||||
0.26 | 0.015 | HLM | Amo | Teng et al., 2010 | |||||
1.4 | 16 | HLM | Amo | Jenkins et al., 2011 | |||||
10.1 | 0.041 | HLM | Amo | VandenBrink et al., 2011 | |||||
21.3 | 0.050 | HLM | Monte | VandenBrink et al., 2011 | |||||
35 | 0.022 | HLM | Pacli | VandenBrink et al., 2011 | |||||
33.6 | 0.082 | HLM | Pio | VandenBrink et al., 2011 | |||||
18.4 | 0.035 | HLM | Repa | VandenBrink et al., 2011 | |||||
48.5 | 0.071 | HLM | Rosi | VandenBrink et al., 2011 | |||||
10.34–25.4 | 0.104–0.25 | HLM | Amo | Korzekwa et al., 2014 | |||||
Gemfibrozil d6-1-O-β glucuronide | Drug metabolite, Deuterated | 29 | 0.033 | rCYP2C8 | Amo | Baer et al., 2009 | |||
Isoniazid | Antituberculosis | Quasi-irreversible | 374 | 0.042 | rCYP2C8 | Pacli | Polasek et al., 2004 | ||
170 | 0.012 | HLM | Pacli | Polasek et al., 2004 | |||||
Lu AA34893 carbamoyl glucuronide | Drug Metabolite | 8.5 | 8.4 | HLM | n/a | Kazmi et al., 2010 | |||
O-methylgemfibrozil acyl-β-d-glucuronide | Gemfibrozil Acyl-β-d-glucuronide Analog | 17 | 3.2 | HLM | Amo | Jenkins et al., 2011 | |||
Nortriptyline | Antidepressant, TCA | Quasi-irreversible | 49.9 | 0.036 | rCYP2C8 | Pacli | Polasek et al., 2004 | ||
Phenelzine | Antidepressant, MAOI | 1.2 | 0.243 | rCYP2C8 | Pacli | Polasek et al., 2004 | |||
54.3 | 0.17 | HLM | Pacli | Polasek et al., 2004 | |||||
Raloxifene | Antiosteoperotic, SERM | >2 | 0.26 | 0.1 | rCYP2C8 | Pacli | VandenBrink et al., 2012 | ||
Thujopsene | Sesquiterpene | 29.8 | 3.3 | HLM | Amo | Jeong et al., 2014 | |||
Toremifene | Anticancer, SERM | 5.0 | 1.9 | HLM | Pacli | Kim et al., 2011b | |||
Verapamil | Antihypertensive, CCB | Quasi-irreversible | 17.5 | 0.065 | rCYP2C8 | Pacli | Polasek et al., 2004 |
CCB, calcium channel blocker; Hep, hepatocytes: HLM, human liver microsomes; IC50, inhibitor concentration supporting half of the maximal inhibition; KI, inactivation constant; kinact, maximal rate of inactivation; MAOI, monoamine oxidase inhibitor; n/a, not available; PKI, protein kinase inhibitor; rCYP2C8, recombinant CYP2C8, SERM, selective estrogen receptor modulator; SSRI, selective serotonin reuptake inhibitor; TCA, tricyclic antidepressant.
↵a Preinc. IC50 depicts IC50 after preincubation of inhibitor for 30 min with NADPH before addition of substrate, except in the case of demethyldabrafenib where the preincubation time was 20 min.
↵b IC50 shift = reversible IC50/preinc. IC50. An IC50 shift ≥1.5-fold is indicative of metabolism-dependent inhibition.
↵c Amo, amodiaquine N-deethylation; Monte, montelukast 36-hydroxylation; Monte-4, formation of montelukast M4; Pacli, paclitaxel 6α-hydroxylation; Pio; pioglitazone hydroxylation (M-IV); Repa, repaglinide 3′-hydroxylation; Rosi, rosiglitazone N-demethylation.