Table 3.
Probability of ADMET and toxicity profile of products predicted by MetaTox from ZEA α-ZEL and β-ZEL.
| Metabolomic profile of ZEA |
Metabolomic profile of α-ZEL and β-ZEL |
|||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Reaction |
O-Glucuronidation |
S-Sulfation |
Hydrolysis |
O-Glucuronidation |
S-Sulfation |
Hydrolysis |
||||||
| Metabolites |
1z |
2z |
3z |
4z |
5z |
1 ab |
2 ab |
3 ab |
4 ab |
5 ab |
6 ab |
7 ab |
| Probability (Prob) | Prob (%) | Prob (%) | Prob (%) | Prob (%) | Prob (%) | Prob (%) | Prob (%) | Prob (%) | Prob (%) | Prob (%) | Prob (%) | Prob (%) |
| Absorption & Distribution | ||||||||||||
| BBB | 37.65 | 37.65 | 97.05 | 97.05 | 79.17 | 31.47 | 50.00 | 37.65 | 97.00 | 97.04 | 97.00 | 79.17 |
| HIA | 72.33 | 70.65 | 95.94 | 96.20 | 96.75 | 97.50 | 68.84 | 71.40 | 95.72 | 96.97 | 95.90 | 97.43 |
| P-gp substrate | 89.04 | 78.58 | 82.69 | 75.15 | 75.38 | 84.12 | 78.48 | 80.17 | 81.59 | 80.54 | 73.72 | 73.06 |
| Caco-2 permeability | 81.87 | 87.20 | 76.48 | 80.89 | 62.41 | 59.94 | 86.25 | 86.09 | 66.51 | 55.72 | 70.99 | 61.16 |
| LogPapp (cm/s) | −7.85 | −8.24 | −6.58 | −6.97 | −6.51 | −7.96 | −7.57 | −7.42 | −6.29 | −6.14 | −6.69 | −6.16 |
| Metabolism | ||||||||||||
| CYP450 2C9 substrate | 100 | 100 | 79.13 | 59.58 | 59.92 | 60.44 | 79.88 | 80.22 | 58.95 | 61.28 | 61.74 | 61.90 |
| CYP450 2D6 substrate | 87.97 | 88.12 | 86.54 | 86.41 | 86.75 | 83.54 | 87.85 | 87.74 | 85.62 | 86.69 | 85.35 | 86.83 |
| CYP450 3A4 substrate | 63.85 | 64.20 | 60.69 | 61.92 | 50.71 | 57.08 | 64.36 | 63.41 | 62.04 | 60.19 | 63.23 | 51.50 |
| CYP450 1A2 inhibitor | 57.71 | 74.19 | 73.02 | 76.60 | 53.79 | 57.71 | 69.70 | 72.83 | 69.70 | 64.06 | ||
| CYP450 2C9 inhibitor | 92.01 | 82.74 | 84.24 | 89.37 | 92.95 | 92.01 | 82.61 | 81.81 | 82.61 | 79.70 | ||
| CYP450 2D6 inhibitor | 92.29 | 87.55 | 90.45 | 90.07 | 91.41 | 92.29 | 87.62 | 86.89 | 87.62 | 90.48 | ||
| CYP450 2C19 inhibitor | 74.09 | 77.83 | 82.96 | 72.46 | 79.05 | 74.09 | 75.21 | 76.29 | 75.21 | 74.04 | ||
| CYP450 3A4 inhibitor | 73.18 | 84.7 | 64.02 | 76.82 | 73.89 | 73.18 | 75.62 | 78.53 | 75.62 | 61.88 | ||
| Toxicity | ||||||||||||
| AMES toxicity | 68.00 | 66.00 | 73.00 | 66.00 | 79.00 | 85.00 | 67.00 | 70.00 | 68.79 | 76.79 | 60.79 | 74.00 |
| Carcinogens | 65.75 | 65.74 | 88.57 | 88.57 | 77.10 | 66.04 | 61.54 | 65.74 | 62.12 | 64.01 | 62.12 | 75.52 |
| Rat acute toxicity (LD50, mol/kg) | 2.65 | 2.22 | 2.50 | 2.03 | 2.36 | 1.94 | 2.36 | 2.45 | 2.77 | 2.37 | 2.3 | 2.27 |
BBB: blood-brain barrier; HIA: human gastrointestinal absorption; P-gp: P-glycoprotein.