“Holistic” In Silico Methods to Estimate the Systemic and CNS Bioavail-abilities of Potential Chemotherapeutic Agents

A fundamental fact in the drug development process is that physical quantity of chemical substance is needed for experimental determinations. Information that could guide the course of a drug discovery program, in particular the penultimate ADME parameters percent oral bioavailability (percentF) and CNS permeability (BBB) are not explicitly determined until after large capital, human and time resources have been invested in a particular chemical series to produce the substance. To assure better go / no-go decisions and to protect the risks of a process that necessitates a considerable front-loading of resources, project teams are turning to computational methods to estimate these parameters. Herein we provide a detailed review of holistic in silico methods toward the estimation of percentF and BBB. An unbiased description of the scope and limitations of their installation and application will be given in the context of an on going pharmaceutical project.