Table 1.

Properties of Ritonavir and Compounds 1–3

	442 nm band (Fe2+)	Ksa (nM)	Eo,7b (mV)	kfastc (s−1)	Tmd (°C)	IC50e (nM)
ritonavir	+f	51 ± 10f	−350 ± 5f	1.4 ± 0.3f	54.8 ± 0.1	550 ± 50
1	−	22 ± 4	<<-370	1.9 ± 0.3	56.5 ± 0.2	280 ± 40
2	±	570 ± 30	≈ −370	2.2 ± 0.4	54.8 ± 0.1	3400 ± 60
3	+	25 ± 5	−350 ± 5	7.0 ± 0.5	57.2 ± 0.2	130 ± 15

^aSpectral dissociation constant.

^bMidpoint redox potential of the inhibitor-bound CYP3A4. E_o,7 of the ligand-free CYP3A4 is ~−300 mV.⁷

^cRate constant of the fast phase of the ligand binding reaction.

^dMelting temperature of the CYP3A4-inhibitor complex. T_m for the ligand-free CYP3A4 in the absence and presence of 2% DMSO is 52.6 ± 0.1 and 52.1 ± 0.1 °C, respectively.

^eConcentration required for half-maximal inactivation of recombinant CYP3A4.

^fDetermined previously.⁷