TABLE 1

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

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

↵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.