Table 2.
Summary of the TGx-DDI validation results on 48 external test agents.
| Class& | Agents | TGx-DDI | Genotoxicity test | ||||
|---|---|---|---|---|---|---|---|
| PA* | 2DC# | PCA@ | Overall | CD% | AMES | ||
| Class 1 | N-Ethyl-N-Nitrosourea (ENU) | + | + | + | + | + | + |
| Mitomycin (MMC) | + | + | + | + | + | + | |
| Ethyl methanesulfonate (EMS) | + | + | + | + | + | + | |
| Belomycin | + | + | + | + | + | + | |
| Nitrogen mustard | + | + | + | + | + | + | |
| Chlorambucil | + | + | + | + | + | + | |
| Busulfan | – | + | – | + | + | + | |
| Isopropyl methanesulfonate | + | + | + | + | + | + | |
| Hydroquinone | – | + | +/– | + | + | + | |
| Class 2 | 2A: Topoisomerase inhibitors | ||||||
| Doxorubicin | + | + | + | + | + | + | |
| Genistein | + | + | + | + | + | – | |
| Topotecan | + | + | + | + | + | + | |
| Norfloxacin | – | – | – | – | + | – | |
| Ciprofloxacin | +/– | + | + | + | + | – | |
| 2B: Antimetabolites | |||||||
| 5-Fluorouracil (5-FU) | + | + | + | + | + | + | |
| Thioguanine (6-TG) | + | + | + | + | + | – | |
| Thiopurine (6-MP) | – | – | – | – | + | – | |
| Azidothymidine (AZT) | – | – | – | – | + | – | |
| 5-azacytidine (5-AzaC) | – | – | – | – | + | + | |
| Class 3 | 3A: Kinase inhibitors | ||||||
| Dasatinib | + | + | + | + | + | – | |
| Imatinib mesylate | – | – | – | – | + | – | |
| Sorafenib | – | – | – | – | + | – | |
| 3B: Additional compounds | |||||||
| Benomyl | – | – | – | – | + | – | |
| Diethylstilbestrol | – | + | + | + | + | – | |
| Nocodazole | – | – | – | – | + | – | |
| Class 4 | 4A: Kinase inhibitors | ||||||
| Sunitinib maleate | – | – | – | – | – | – | |
| Gefinitib | – | – | – | – | – | – | |
| Progesterone | – | – | – | – | – | – | |
| Diethanolamine | – | – | – | – | – | – | |
| Melamine | – | – | – | – | – | – | |
| 4C: Antibiotics | |||||||
| Ampicillin | – | – | – | – | – | – | |
| Erythromycin Stearate | – | – | – | – | – | – | |
| 4D: Others | |||||||
| D-Mannitol | – | – | – | – | – | – | |
| n-Butyl Chloride | – | – | – | – | – | – | |
| 3-Nitropropionic acid | – | – | – | – | – | – | |
| Methyl Carbamate | + | +/– | + | + | – | – | |
| Class 5 | Phenobarbital | – | – | – | – | + | – |
| Esomeprazole | – | – | – | – | + | – | |
| Donepezil | – | – | – | – | + | – | |
| Cyclohexamide | – | – | – | – | + | – | |
| 2,4 Dinitrophenol (2,4 DNP) | – | – | – | – | + | – | |
| Olmesartan | – | – | – | – | + | – | |
| Exemastan | + | + | + | + | + | – | |
| Rabeprazole-NA | – | – | – | – | + | – | |
| Rotigotin | – | – | – | – | + | – | |
| Dexamethasone | – | – | – | – | + | – | |
| Caffeine | – | – | – | – | + | – | |
| Staurosporine | – | – | – | – | + | – | |
Chemical classes: Class 1, DDI agents that interact directly with DNA; Class 2, DDI agents that interact indirectly with DNA; Class 3, Kinase inhibitors and other compounds that may interact indirectly with DNA, with positive CD findings; Class 4, Non-genotoxic agents; Class 5, Agents with irrelevant positives for in vitro assays.
PA, Probability Analysis.
2DC, 2-Dimensional Clustering.
PCA, Principle Component Analysis.
CD, Chromosomal Damage Assay.
Validated chemicals are listed by classes. The column “TGx-DDI” shows results from the three analysis methods and the “Overall” prediction (positive in any one = +; negative in all three = –). The column “Genotoxicity tests” includes the results of CD and the Ames assay documented elsewhere.