ADME and Multimechanism Screens

In silico property prediction is needed more than ever to cope with the screening overload. Improved prediction technologies are continuing to emerge [13,14]. However, reliably measured physicochemical properties to use as training sets for new target applications have not kept pace with the in silico methodologies. 

Prediction of ADME properties should be simple, since the number of descriptors underlying the properties is relatively small, compared to the number associated with effective drug-receptor binding space. In fact, prediction of ADME is difficult The current ADME experimental data reflect a multiplicity of mechanisms, making prediction uncertain. Screening systems for biological activity are typically single mechanisms, where computational models are easier to develop [1], 

Compounds from traditional drug space ( common drugs —readily available from chemical suppliers), often chosen for studies by academic laboratories for assay validation and computational model-building purposes, can lead to misleading conclusions when the results of such models are applied to real discovery compounds, which most often have extremely low solubilities [16]. 

The subject of this book is to examine the components of the multimechanistic processes related to solubility, permeability, and charge state, with the aim of advancing improved strategies for in vitro assays related to drug absorption. 

---