High-Throughput Screening

GastroPlus gives you the ability to assess the relative gastrointestinal absorption of a large number of compounds in a short period of time. In Batch Simulations mode, the predicted absorption for many thousands of potential drug compounds can be generated in a single day, once the input data is set up.

Researchers use both in vitro and in vivo experiments to guide the discovery phase. GastroPlus can help to focus experimental efforts by providing information regarding what experiments are needed to provide important absorption data and what experiments might be eliminated without adverse effects.

For example, suppose you have a large number of theoretical molecules described as SMILES structures, but you have not yet synthesized and characterized them. In order to run GastroPlus, you will need to input the following values for each molecule: effective permeability; logP or logD(pH); pKa; diffusion coefficient; solubility; and pH at which the solubility was measured. Determining these numbers accurately for many thousands of compounds would incur significant time and expense in the lab.

With the ADMET Predictor Module, you can generate estimates for the inputs needed by GastroPlus from chemical structure. While most of these predictions are accurate, variations between measured and predicted values can sometimes be large.

Running GastroPlus in the Parameter Sensitivity Analysis mode, you can run sensitivity studies to provide an indication of which estimated molecular parameters have the greatest effect on predicted absorption. For example, if it is shown that, for certain drugs of interest, solubility has little effect, then there would be no need to run solubility experiments. On the other hand, if variations in solubility were shown to be significant for certain other drugs, then experiments to determine solubility accurately would be warranted for those drugs.