P-glycoprotein (P-gp) is an ATP driven efflux pump encoded by the MDR1 gene, capable of transporting a wide spectrum of chemical structures as well as different classes of drugs. Active transport by P-gp can represent a serious hurdle for pharmaceuticals as transport by P-gp has been associated with reduced bioavailability of orally administered drugs and with decreased ability of drug candidates to cross blood-tissue barriers such as the blood-brain barrier. In addition, if a drug is subject to significant P-gp efflux, its distribution, absorption and elimination could be altered by potent P-gp inhibitors leading to drug-drug interactions. Therefore, from the drug discovery and development perspective, knowledge of the transport of drug candidates by P-gp is desirable at an early stage of the drug design process.
These models are based on data sets published by Zdrazil et al. (Mol. Inf. 31(8), pp. 599–609 (2012)) in a review of public domain data from assays of P-gp efflux activity. Two data sets have been used, one classifying compounds as P-gp inhibitors or non-inhibitors, the second containing pEC50 data from a daunorubicin transport assay in MDR CCRF vcr1000 cells.
| Modelling method | Training set | Validation set | Test set | |||
| Accuracy | Kappa | Accuracy | Kappa | Accuracy | Kappa | |
| Random forest | 1 | 1 | 0.93 | 0.86 | 0.86 | 0.71 |
| Modelling method | Training set | Validation set | Test set | |||
|---|---|---|---|---|---|---|
| R2 | RMSE | R2 | RMSE | R2 | RMSE | |
| GP Opt | 0.93 | 0.30 | 0.70 | 0.61 | 0.60 | 0.50 |
Full details of the models, data sets and detailed outputs from the modelling process may be downloaded.
To use these within StarDrop, download and save these files in a convenient place.
Load them into StarDrop using the button on the Models tab.
Alternatively, the directory in which the model files have been saved can be added to the paths from which models are automatically loaded when StarDrop starts by selecting the File->Preference menu option and adding the directory under Models in the File Locations tab.
Full details of the models, data sets and detailed outputs from the modelling process may be downloaded.
To use these within StarDrop, download and save these files in a convenient place.
Load them into StarDrop using the button on the Models tab.
Alternatively, the directory in which the model files have been saved can be added to the paths from which models are automatically loaded when StarDrop starts by selecting the File->Preference menu option and adding the directory under Models in the File Locations tab.
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