Table 1.
IC50 and 95% confidence intervals (CI) of select CYP2B6 and CYP3A4 inhibitors.
| CYP2B6 |
CYP3A4 |
||||||
|---|---|---|---|---|---|---|---|
| Chemical | IC50(µM) | 95% CI (µM) | Hillslope | IC50 (µM) | 95% CI (µM) | Hillslope | IC50 Ratio1 |
| Fatty acids | |||||||
| Arachidonic acid | 1.04 | 0.20–5.35 | −0.59 | 13.7 | 7.21–21.62 | −4.08 | + 13.2 |
| Docosahexaenoic acid | 2.06 | 1.30–3.27 | −1.22 | 5.08 | 2.66–9.69 | −5.0 | + 2.47 |
| α-Linolenic acid | 7.32 | 5.91–9.30 | −1.45 | 4.04 | 0.427–38.3 | −0.701 | − 2.36 |
| Linoleic acid | 9.19 | 5.23–16.1 | −0.69 | 18.3 | 10.10–33.10 | −4.46 | + 1.99 |
| Oleic acid | 9.30 | 7.18–12.10 | −2.45 | np | np | np | np |
| Palmitic acid | nd | nd | nd | 19,890 | nd | nd | nd |
| Bile acids and steroids | |||||||
| Chenodeoxycholic acid | 49.0 | 48.3–62.8 | −1.32 | np | np | np | np |
| Lithocholic acid | 2.47 | 0.924–6.61 | −0.51 | 3233 | 3.5E-6–2.9E7 | −3.26 | +1313 |
| Testosterone | 90.2 | 64.4–126.4 | −0.32 | 33.9 | 12.53–91.52 | −4.73 | −2.66 |
| Estradiol | 42.2 | 24.8–71.6 | −0.33 | 2.78 | 0.617–12.5 | −0.903 | −15.2 |
| Pesticides | |||||||
| Endosulfan | 0.0030 | 0.0024–0.0037 | −0.66 | 0.00460 | 0.0025–0.0086 | −0.261 | +1.53 |
| Parathion | 0.026 | 0.021–0.032 | −1.13 | 0.729 | 0.369–1.439 | −0.094 | +28.03 |
| Atrazine | 0.144 | 0.022–0.952 | −0.34 | nd | nd | nd | +++ |
| Cypermethrin | 6040 | nd | −0.79 | np | np | np | np |
| Chlorpyrifos | 0.0092 | 0.0087–0.0097 | −2.09 | 0.280 | 0.0050–1.57 −0.507 | +30.4 | |
| Diazinon | 0.0754 | 0.0675–0.0840 | −1.51 | 0.0665 | 0.022–0.199 | −2.52 | −1.13 |
| Other chemicals | |||||||
| (+)-α-Pinene | 292 | 2.0E-12–4.2E16 | −1.74 | np | np | np | np |
| Buproprion | 50.7 | 2.74–9.4E4 | −0.70 | np | np | np | np |
| Ticlopidine | 0.0196 | 0.0174–0.0219 | −0.95 | nd | nd | nd | nd |
| Phthalic acid | 1170 | nd | −1.71 | np | np | np | np |
| Bisphenol A | 8.44 | 6.50–10.90 | −2.65 | np | np | np | np |
| Nonylphenol | 0.221 | 0.185–0.263 | −1.21 | 6.25 | 4.43–8.81 | −1.02 | + 28.30 |
| Triclosan | 0.944 | 0.693–1.28 | −1.30 | 2.39 | 1.80–3.17 | −1.46 | + 2.53 |
| Jet fuel | 0.171 | 0.062–0.458 | −0.08 | np | np | np | np |
1
Ratio: is the ratio of the IC50 values from the two CYPs. + indicates greater affinity for CYP2B6 and – indicates greater affinity for CYP3A4.
np: Assay not performed
nd: Parameters were not determined because of poor inhibition.
All chemicals with an IC50 below 5.0 µM for CYP2B6 were also investigated for CYP3A4 inhibition.
Statistics determined using GraphPad Prism 7.0 as described in materials and methods (San Diego, CA).