"Holistic" in silico methods to estimate the systemic and CNS bioavailabilities 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 % oral bioavailability (%F) 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 %F 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.