In silico ADME: rule-based systems

ALAN TALEVI

The ADME Encyclopedia. A Comprehensive Guide on Biopharmacy and Pharmacokinetics

Springer Nature

Año: 2022; p. 531 - 537

ADME rule-based approaches are hard-logic in silico tools used during the early drug discovery and development stages (hit and lead identification stages) to perform a cost-efficient, automated ADME profiling, focusing on those regions of the chemical space more likely to result in a successful drug discovery and development project. They are based on rules-of-thumb and structure alerts [1], and strongly related to the concepts of drug-likeness and lead-likeness. Rule-based approaches have been substantially developed and adopted within the pharmaceutical sector after the pioneering work of Christopher Lipinski and his coworkers at Pfizer, who implemented the popular ?rule of five? [2]. Rules-of-thumb decision making is well aligned with the ?fail early, fail cheap? (or ?fail fast, fail cheap?) principle. Although not without limitations, the application of this paradigm might have significantly contributed to the sharp drop in drug projects terminated due to pharmacokinetic reasons between 1990s and 2000s [3, 4].