TABLE 1.
AhR activity: gene reporter assay and AZ-AHR cells (n = 2)
PubChem Bioassay AID2796 (https://pubchem.ncbi.nlm.nih.gov/bioassay/2796): “Luminescence-based primary cell-based high throughput screening assay to identify activators of the Aryl Hydrocarbon Receptor (AHR)”; relative efficacy = 100 × fold induction (200 μM compound)/fold induction (10 nM TCDD); relative potency = 100 × EC50 TCCD/EC50 compound.
| Compound | CID | AID2796 | Relative Efficacy |
EC50 (Exp1/Exp2) |
Relative Potency |
IC50 (Exp1/Exp2) |
||||
|---|---|---|---|---|---|---|---|---|---|---|
| 8 hours | 24 hours | 8 hours | 24 hours | 8 hours | 24 hours | 8 hours | 24 hours | |||
| % | % | % | % | |||||||
| 1-Methylindole | 11781 | Not tested | 6.8–11.1 | 2.7–3.0 | N.C. | N.C. | N.C. | N.C. | 103.7 (CI 77.7–138.6 μM)/191.1 μM (CI 133.2–274.1 μM) | >200 μM |
| 2-Methylindole | 7224 | Not tested | 8.7–11.3 | <2 | N.C. | N.C. | N.C. | N.C. | 73.8 (CI 60.6–88.9 μM)/56.3 μM (CI 46.7–68.0 μM) | 68.0 (CI 52.1–88.6 μM)/62.9μM (CI 49.2–80.4 μM) |
| 3-Methylindole | 6736 | Inactive | 24.3–27.6 | 2.5–6.7 | 12.4 (CI 7.5–20.3 μM)/19.8 μM (CI 11.4–34.3 μM) | 66.5 (CI 57.3–77.1 μM)/84.9 μM (CI 63.9–112.7 μM) | 0.0029 | 0.0193 | Potentiation | 20.1 (CI 13.2–30.7 μM)/18.3 μM (CI 15.5–21.6 μM) |
| 4-Methylindole | 85262 | Not tested | 31.9–76.0 | 110.1–156.9 | 16.3 (CI 10.2–26.1 μM)/12.7 μM (CI 7.2–22.2 μM) | 47.3 (CI 42.2–52.8 μM)/47.7 μM (CI 36.8–61.8 μM) | 0.0163 | 0.0065 | Potentiation | Potentiation |
| 5-Methylindole | 1197B | Not tested | 62.0–80.3 | 19.9–21.6 | 43.6 (CI 31.1–61.0 μM)/38.0 μM (CI 23.7–60.8 μM) | N.C. | 0.0054 | N.C. | Potentiation | 161.5 (CI 126.8–205.7 μM)/153.1 μM (CI 121.4–193.2 μM) |
| 6-methylindole | 137928 | Not tested | 16.6–35.5 | 74.6–106.4 | 39.6 (CI 22.9–68.3 μM)/28.5 μM (CI 14.2–57.4 μM) | N.C. | 0.0065 | N.C. | Potentiation | Potentiation |
| 7-Methylindole | 70275 | Not tested | 45.5–49.1 | 6.0–7.1 | 36.9 (CI 19.2–71.0 μM)/36.0 μM (CI 20.6–62.8 μM) | N.C. | 0.0060 | N.C. | Potentiation | 35.0 (CI 29.5–41.5 μM)/41.0 μM (CI 29.7–56.8 μM) |
| 1,2-di-methylindole | 13408 | Not tested | 18.6–19.5 | <2 | 69.0 (CI 54.2–87.6 μM)/72.3 μM (CI 59.9–87.2 μM) | 50.9 (CI 32.7–79.2 μM)/70.8 μM (CI 46.1–108.9 μM) | 0.0031 | 0.0051 | >200 μM | 227.7 (CI 167.5–309.5 μM)/159.3 μM (CI 117.6–215.7 μM) |
| 1,3-Di-methylindole | 70130 | Not tested | 22.9–24.2 | <2 | 58.6 (CI 46.6–73.8 μM)/63.9 μM (CI 52.3–78.0 μM) | N.C. | 0.0036 | N.C. | >200 μM | >200 μM |
| 2,3-Di-methylindole | 7053 | Not tested | 48.7–49.1 | 7.4–12.8 | N.C. | N.C. | N.C. | N.C. | 14.6 (CI 11.7–18.2 μM)/10.2 μM (CI 6.9–15.2 μM) | 8.9 (CI 7.3–10.9 μM)/12.1 μM (CI 5.4–27.0 μM) |
| 2,5-Di-methylindole | 70965 | Not tested | 47.1–68.8 | 18.6–29.9 | 11.0 (CI 6.3–19.0 μM)/55.1 μM (CI 29.8–101.9 μM) | N.C. | 0.0066 | N.C. | Potentiation | >200 μM |
| 2,3,3-Tri-methylindolenine | 15427 | Not tested | <2 | <2 | N.C. | 70.6 (CI 64.3–77.5 μM)/42.2 μM (CI 28.3–65.2 μM) | N.C. | 0.0055 | 106.1 (CI 96.4–116.8 μM)/70.2 μM (CI 41.3–119.3 μM) | >200 μM |
| 2,3,7-Tri-methylindole | 96869 | Not tested | 6.6–7.0 | <2 | N.C. | N.C. | N.C. | N.C. | 23.4 (CI 14.7–37.2 μM)/29.5μM (CI 16.8–51.8 μM) | 11.0 (CI 9.2–13.2 μM)/13.l μM (CI 10.5–16.2 μM) |
| 4-Methoxyindole | 138363 | Not tested | 4.0–4.5 | <2 | N.C. | N.C. | N.C. | N.C. | >200 μM | >200 μM |
| 5-Methoxyindole | 13872 | Not tested | 10.4–13.0 | <2 | N.C. | N.C. | N.C. | N.C. | >200 μM | >200 μM |
| 6-Methoxyindole | 76659 | Inactive | 37.3–38.6 | <2 | N.C. | N.C. | N.C. | N.C. | >200 μM | 67.8 (CI 51.4–89.6 μM)/76.7 μM (CI 67.7–86.9 μM) |
| 7-Methoxyindole | 76660 | Not tested | 23.1–24.7 | 78.8–81.3 | 8.8 (CI 5.8–13.4 μM)/6.2 μM (CI 4.6–8.3 μM) | 57.9 (CI 53.0–63.3 μM)/49.5 μM (CI 47.9–51.2 μM) | 0.0293 | 0.0058 | Potentiation | Potentiation |
| 4,6-Di-methoxyindole | 828760 | Inactive | 2.3–3.3 | 2.0 ± 3.5 | 2.3 (CI 1.6–3.3 μM)/5.9 μM (CI 4.1–8.5 μM) | 68.5 (CI 55.5–84.5 μM)/49.7 μM (CI 38.6–64.3 μM) | 0.0537 | 0.0052 | 132.1 (CI 87.1–200.4 μM)/180.5 μM (CI 144.8–225.0 μM) | >200 μM |
| 5,6-Di-methoxyindole | 84431 | Not tested | <2 | <2 | N.C. | 22.6 (CI 7.4–68.9 μM)/28.2 μM (CI 18.1–43.9 μM) | N.C. | 0.0122 | 178.1 (CI 125.4–252.9 μM)/192.1 μM (CI 117.2–314.8 μM) | >200 μM |
| 4-Methoxy-l-Me-indole | 595238 | Not tested | 13.3–18.5 | <2 | 26.5 (CI 19.2–36.8 μM)/46.7 μM (CI 36.1–60.4 μM) | 59.3 (CI 44.3–79.5 μM)/74.5 μM (CI 56.3–98.6 μM) | 0.0059 | 0.0046 | 107.0 (CI 84.6–135.2 μM)/174.1 μM (CI 42.4–714.1 μM) | 210.4 μM (CI 145.8– 303.6 μM)/162.0 μM (CI 141.7–185.3 μM) |
| 5-Methoxy-2-Me-indole | 70642 | Not tested | <2 | <2 | N.C. | 15.3 (CI 10.4–22.5 μM)/6.0 μM (CI 3.3–11.0 μM) | N.C. | 0.0292 | 22.9 (CI 17.8–29.4 μM)/17.1 μM (CI 13.3–21.9 μM) | 55.8 (CI 39.0–79.7 μM)/37.6 μM (CI.28.9–48.9 μM) |
| TCDD | — | 1000 | 100 | 2.1 (CI 1.6–2.8 nM)/2.3 nM(CI 2.1–2.5 nM) | 3.1 (CI 2.2–4.4 nM)/3.1 nM(CI 2.7–3.6 nM) | 100 | 100 | — | ||
CI, confidence interval; CID, compound identification (PubChem); Exp1, experiment 1; Exp2, experiment 2; N.C., not calculated.