TABLE 3.

PLSR predictions of change in potency towards six P450 isoforms as a function of 16 chemical features, calculated for the compounds in S₆₄

Feature	2C8	3A4	2D6	2C9	1A2	2C19
<25 Heavy atoms	−0.03 a	−0.13	0.03	0.00	0.06	0.07
25–45 Heavy atoms	0.10	0.09	0.06	0.06	−0.04	0.01
>45 Heavy atoms	−0.14	0.07	−0.16	−0.10	−0.03	−0.14
Positive charge	−0.14	−0.14	−0.04	−0.12	−0.05	−0.05
Negative charge	0.12	−0.03	−0.25	0.18	−0.29	−0.21
1 Ring	0.02	−0.04	0.17	−0.02	−0.05	0.13
2 Fused rings	0.16	0.02	0.16	0.00	0.03	0.14
3 Fused rings	0.00	−0.11	0.30	−0.11	0.36	0.25
4 + Fused rings	0.11	−0.07	0.10	0.11	−0.27	0.09
Ester	−0.02	−0.06	−0.25	−0.10	−0.26	−0.10
Ether	−0.16	−0.09	0.03	−0.15	0.13	−0.05
Acid	−0.21	0.02	0.04	−0.12	0.02	0.01
Secondary amine	−0.08	0.18	0.06	−0.08	−0.02	−0.04
Tertiary amine	0.02	0.13	0.15	−0.08	−0.46	−0.06
Nitroaromatic	0.23	0.18	0.24	0.21	0.48	0.27
Azole	0.25	0.43	0.00	0.31	0.06	0.31

^a Italics indicate values <0, i.e., presence of a feature correlates with lower potency (higher IC₅₀) towards a particular isoform. A value of 0.5 corresponds to a 10^0.5 = 3.2-fold decrease in IC₅₀.