TABLE 1.

Selectivity of inhibitors of CYP2A enzymes as evaluated by binding affinity and inhibitor dissociation constants

Inhibitor	P450	Kd (Binding Mode)a	2A13 Kd/2A6 Kd	Kid	Mechanism (α Value)	2A13 Ki/2A6 Ki
		μM		μM
Tranylcypromine	2A13	2.3 (II)	1.2	6.5 ± 1.2	Competitive	49
	2A6	2.0 (II)		0.13 ± 0.02	Mixed (α = 10)
(R)-Menthofuran	2A13	0.58 (I)	0.13	54 ± 12	Mixed (α = 4.3)	27
	2A6	4.5 (I)		2.0 ± 0.44	Mixed (α = 4.3)
Tryptamine	2A13	5.2 (II)	2.3	16 ± 3.5	Competitive	9.4
	2A6	2.3 (II)		1.7 ± 0.12	Competitive
DMABA	2A13	0.65 (I)	0.96	17 ± 5.0	Mixed (α = 13)	4.6
	2A6	0.68 (I)		3.6 ± 0.83	Mixed (α = 5.5)
PEITC	2A13	0.43 (I)b	0.064	3.8 ± 1.6	Mixed (α = 0.20)	2.2
	2A6	6.2 (I)b		1.7 ± 0.28	Mixed (α = 270)
β-Nicotyrine	2A13	8.2 (I)	0.12	5.6 ± 0.86	Mixed (α = 6.6)	0.74
	2A6	71 (I)		7.5 ± 2.9	Mixed (α = 3.5)
(S)-Nicotine	2A13	54 (I)	0.11	72 ± 4.6	Competitive	0.55
	2A6	470 (I)		130 ± 8.8	Competitive
Pilocarpine	2A13	3.0 (II)c	0.83	1.4 ± 0.12	Competitive	0.47
	2A6	3.6 (II)c		3.0 ± 0.45	Mixed (α = 25)
8-MOP	2A13	1.6 (I)	0.14	0.040 ± 0.009	Mixed (α = 1.9)	0.16
	2A6	11 (I)		0.25 ± 0.10	Mixed (α = 3.3)

^a The binding modes are shown in parentheses, where (I) represents type I binding and (II) represents type II binding.

^b DeVore et al., 2009.

^c DeVore et al., 2012.

^d K_i ± S.E.