Table 1

Examples of activation kinetics (heterotropic positive cooperativity) reported in the literature in various in vitro systems

Effector	Substrate	Pathway	Enzyme Source	Reference
7,8-Benzoflavone	Aflatoxin B1	8,9-Epoxidation	E. coli-purified CYP3A4	Ueng et al., 1997
7,8-Benzoflavone	Carbamazepine	10,11-Epoxidation	E. coli-purified CYP3A4	Ibid.
7,8-Benzoflavone	Phenanthrene	Hydroxylation	HepG2-expressed CYP3A4	Shou et al., 1994
7,8-Benzoflavone	Phenanthrene	Hydroxylation	HepG2-expressed CYP3A4	Korzekwa et al., 1998
7,8-Benzoflavone	Benzo[a]pyrene	Hydroxylation	RLM	Wiebel et al., 1971
7,8-Benzoflavone	Benzo[a]pyrene	Hydroxylation	HLM	Kapitulnik et al., 1977
7,8-Benzoflavone	Progesterone	6β-Hydroxylation	HLM	Schwab et al., 1988
7,8-Benzoflavone	17β-Estradiol	2-Hydroxylation	HLM	Ibid.
7,8-Benzoflavone	Diazepam	Hydroxylation	HLM	Andersson et al., 1994
7,8-Benzoflavone	Diazepam	N-Demethylation	HLM	Ibid.
7,8-Benzoflavone	Phenacetin	O-Deethylation	HLM	Nakajima et al., 1999
Dapsone	Flurbiprofen	4′-Hydroxylation	Baculovirus-purified CYP2C9	Korzekwa et al., 1998
Dapsone	Flurbiprofen	4′-Hydroxylation	Baculovirus-expressed CYP2C9	Hutzler et al., 2001b
Dapsone	Naproxen	O-Demethylation	Baculovirus-expressed CYP2C9	Ibid.
Dapsone	Piroxicam	5′-Hydroxylation	Baculovirus-expressed CYP2C9	Ibid.
Quinidine	Meloxicam	5′-Methylhydroxylation	HLM and B-lymphoblastoid-expressed CYP3A4^1-a	Ludwig et al., 1999
Quinidine	Diclofenac	5-Hydroxylation	HLM and B-lymphoblastoid-expressed CYP3A4^1-a	Ngui et al., 2000
Quinidine	Warfarin	4′- and 10-hydroxylation	HLM and B-lymphoblastoid-expressed CYP3A4^1-a	Ngui et al., 2001
Testosterone	Midazolam	4-Hydroxylation	HLM and B-lymphoblastoid-expressed CYP3A4^1-a	Wang et al., 2000
Testosterone	Diazepam	3-Hydroxylation N-Demethylation	B-Lymphoblastoid-expressed CYP3A4	Kenworthy et al., 2001
Testosterone	Midazolam	4-Hydroxylation	HLM	Maenpaa et al., 1998

RLM, rat liver microsomes; HLM, human liver microsomes.
↵1-a Obtained from GENTEST (Woburn, MA).