A hierarchical screening methodology for physicochemical/ADME/Tox profiling

Abstract

Full integration of pharmaceutical profiling into pharmaceutical lead selection and optimisation requires that complete sets of unequivocal data be available at the time compound design or advancement decisions are made. As the productivity of chemical synthesis expands, and the breadth of profiling assays grow in scope, physicochemical/ADME/Tox laboratories are being challenged to produce ever more data to support an accelerating decision cycle. This article focuses on the challenges of increasing preclinical profiling productivity while managing lower accuracy higher throughput data streams to preserve confidence in decision making. The authors propose a hierarchical screening strategy and describe the implementation of an automated system designed to support that strategy efficiently.

Keywords::

• ADME/Tox
• automation
• CYP inhibition
• informatics
• LogP
• metabolic stability
• PADMET
• protein binding
• screening
• software
• solubility