Table 2.
Summary of predicted and experimental data for sample ToxCast data set compounds.
| Compound | Docking classificationa | Bayesian score (classification) | U.S. EPA ToxCast (NCGC) hPXR DPX-2 classification [EC50 (μM)]b | HepG2 hPXR EC50 (μM)c | Efficacy relative to 10 μM rifampicinc | Cell viability IC50 (μM)c | DPX-2 hPXR EC50 (μM)c |
|---|---|---|---|---|---|---|---|
| Mancozeb | N | −7.253 (N) | N | X | |||
| Mesosulfuron-methyl | A | −1.589 (A) | N | X | X | X | |
| Diethylhexyl phthalate | A | 1.943 (A) | A (20.75) | 1.8 (S) | 0.63 | ||
| Methyl hydrogen phthalate | N | 1.868 (A) | N | ||||
| Bensulide | A | −1.165 (A) | A (1.57) | ||||
| Foramsulfuron | A | −1.653 (A) | N | > 50 (W) | |||
| Bensulfuron methyl | A | 0.601 (A) | N | 89.4 (W) | 0.18 | X | X |
| Esfenvalerate | A | 5.796 (A) | A (26.98) | 1.5 (S) | 0.64 | X | 8.94 (S) |
| Z,E-fenpyroximate | A | 2.613 (A) | N | X | 0.04 | 32.74 (M) | |
| Butafenacil | A | 3.317 (A) | N | 6 (S) | 0.53 | ||
| α-Cypermethrin | A | 5.346 (A) | A (18.3) | 1.6 (S) | 0.54 | X | 0.88 (S) |
| Triflusulfuron methyl | A | −1.998 (A) | N | – | |||
| β-Cyfluthrin | A | 5.346 (A) | A (19.7) | 2.5 (S) | 0.54 | > 100 | 18.2 (M) |
| Permethrin | A | 4.83 (A) | A (20.26) | 5.4 (S) | 0.53 | X | 29.09 (M) |
| Oxasulfuron | A | −1.942 (A) | N | ||||
| Fenarimold | N | 4.791 (A) | A (20.29) | ||||
| Propiconazoled | A | 3.475 (A) | A (36.81) | ||||
| Fenbuconazoled | A | 5.390 (A) | N | ||||
| Prochlorazd | A | 2.705 (A) | N | ||||
| Imazalild | N | 3.466 (A) | A (36.54) | ||||
| Oxadiazond | A | 4.663 (A) | A (5.49) | ||||
| Alachlord | N | 7.842 (A) | A (15.35) | ||||
| 2,4-Dd | N | −0.563 (A) | N | ||||
| Diurond | N | 4.357 (A) | N | ||||
| Atrazined | N | −2.825 (A) | N | ||||
| Fipronild | N | −0.033 (A) | A (12.55) | ||||
| Thiabendazoled | N | 2.879 (A) | N | ||||
| Carbaryld | N | 1.265 (A) | N |
Abbreviations: 2,4-D, 2,4-dichlorophenoxyacetic acid; A, agonist; M, medium agonist; N, nonagonist; S, strong agonist; W, weak agonist; X, no activity measurable. Values with Bayesian scores greater than −5.792 were classed as PXR agonists based on the model output (Ekins et al. 2009). Docking classification was performed using GoldScore, with cutoff values listed in Table 1. Agonists were classified based on the following criteria used in a previous study (Ekins et al. 2008b): S, EC50 < 10 μM; M, EC50 11–50 μM; W, EC50 > 50 μM (but with activation at least 10% that of 10 μM rifampicin).
Based on data provided in Supplemental Material, Table 1 (doi:10.1289/ehp.1001930).
For NCGC data (Judson et al. 2010), the cutoff for activity was 200 μM.
Assays performed in the present study.
Componds with previously published data generated in HeLa cells (Lemaire et al. (2006).