In silico ADME/Tox: why models fail.
By way of example, we discuss the apparent 'failure' of in silico ADME/Tox models and attempt to understand the causes. Often, the interpretation of the success of models lies in their use and the expectations of the user. Other times, models are, in fact, of little value. Disappointing results can be linked to the key aspects of the model and modeling procedure, many of these related to the original data and its interpretation. We make recommendations to providers of models regarding the development, description, and use of models as well as the data and information that are important to understanding a model's quality and scope of use.
D002352:Carrier Proteins / Q000378:metabolism; D027682:Cation Transport Proteins; D002463:Cell Membrane Permeability; D002478:Cells, Cultured / Q000187:drug effects; D003110:Colonic Neoplasms / Q000473:pathology; D003198:Computer Simulation; D017076:Computer-Aided Design / Q000592:standards; D065690:Cytochrome P-450 CYP2D6 Inhibitors; D004268:DNA-Binding Proteins; D015195:Drug Design; D004353:Drug Evaluation, Preclinical; D000072237:ERG1 Potassium Channel; D004791:Enzyme Inhibitors / Q000494:pharmacology; D051638:Ether-A-Go-Go Potassium Channels; D006801:Humans; D016014:Linear Models; D008954:Models, Biological; D018408:Patch-Clamp Techniques; D010599:Pharmacokinetics; D026902:Potassium Channel Blockers / Q000494:pharmacology; D015221:Potassium Channels / Q000187:drug effects; D024642:Potassium Channels, Voltage-Gated; D012995:Solubility; D015534:Trans-Activators; D000071230:Transcriptional Regulator ERG
D002352:Carrier Proteins; D027682:Cation Transport Proteins; D065690:Cytochrome P-450 CYP2D6 Inhibitors; D004268:DNA-Binding Proteins; C072312:ERG protein, human; D000072237:ERG1 Potassium Channel; D004791:Enzyme Inhibitors; D051638:Ether-A-Go-Go Potassium Channels; C092509:KCNH6 protein, human; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D024642:Potassium Channels, Voltage-Gated; D015534:Trans-Activators; D000071230:Transcriptional Regulator ERG