Table 1.

Properties of the CYP3A4 inhibitors

compound	λmax (nm)		A421/417a	A443/417b	Ksc μM	IC50d μM	IC50/Ks	ΔTme °C	kfastf s−1	fast phaseg %	ΔA427nmh %
	ferric	ferrous
5a	421	443	1.12	0.82	12 ± 2	27.8 ± 2.6	2.3	0.2	1.4±0.2	41	38
5b	421	443	1.07	0.81	5 ± 1	10.8 ± 0.5	2.2	0.7	1.4±0.3	50	55
5c	422	443	1.03	0.66	1.8 ± 0.2	2.3 ± 0.1	1.3	0.5	1.6±0.1	55	74
8a	421	442	1.02	0.58	0.92 ± 0.02	3.9 ± 0.2	4.2	0.4	1.0±0.1	55	64
8b	421	442	1.05	0.56	0.42 ± 0.03	1.96 ± 0.08	4.7	0.9	1.4±0.1	48	78
8c	422	443	1.07	0.76	0.11 ± 0.01	0.72 ± 0.03	6.5	0.8	1.9±0.2	59	96
8d	421	443	1.12	0.77	0.78 ± 0.03	0.97 ± 0.06	1.2	1.0	1.6±0.2	53	93
8e	421	443	1.05	0.81	0.11 ± 0.01	0.66 ± 0.03	6.0	1.4	1.6±0.1	55	94
8f	421	443	1.05	0.87	0.08 ± 0.01	0.43 ± 0.02	5.4	1.1	2.4±0.3	54	100
ritonavir	421	442	1.08	1.10	0.017± 0.003	0.32 ± 0.04	18.8	0.9	1.2±0.1	60	100
15ai	421	442	1.02	0.81	0.9	0.52	0.6	−1.0	1.7	55	n.d.j
15bi	421	442	1.00	0.87	0.5	0.21	0.4	0.2	8.0	57	n.d.

^{a, b}Ratios between the absorbance maxima for the ferric and ferrous ligand-bound forms and the Soret band of ferric ligand-free CYP3A4, respectively.

^cThe dissociation constant for the CYP3A4-inhibitor complex determined from the titration plots shown in Insets in Figure 3.

^dDetermined for the BFC debenzylase activity of recombinant CYP3A4 in a reconstituted system with CPR.

^eLigand-dependent changes in the melting temperature of CYP3A4.

^fThe rate constant for the fast and slow kinetic phase of the CYP3A4-ligand binding reaction determined at saturating ligand concentration.

^gPercentage of the absorbance change taking place during the fast kinetic phase.

^hPercentage of the maximal absorbance change observed at the end of the reaction.

ⁱCharacterized previously.²¹

^jNot determined.