Addressing Toxicological Issues in the Lead‐Optimization Phase of Drug Discovery and Development
Philip Bentley · 2001
The advent of combinatorial chemistry and the availability of rapid screening methods to detect compounds with desired pharmacological properties have altered the dynamics of the drug-discovery process. The great diversity of potential lead structures generated in the early research phase results in a desire for methods to rapidly screen for undesirable effects, and for computer models to determine structure-toxicity relationships. This new situation presents a tremendous challenge to toxicologists working in drug discovery. The number of potential toxicological effects is almost as great as that of pharmacological endpoints, and developing screens for the plethora of toxicities is essentially impossible. Toxic effects may be broadly classified into a few distinct categories.