Progress and problems in the exploration of therapeutic targets.

Drugs exert their therapeutic effect by binding and regulating the activity of a particular protein or nucleic acid target. A large number of targets have been explored for drug discovery. Continuous effort has been directed at the search for new targets and more-extensive exploration of existing targets. Knowledge of these targets facilitates the understanding of molecular mechanisms of drugs and the effort required for drug discovery and target searches. Areas of progress, current focuses of research and development and the difficulties in target exploration are reviewed. The characteristics of the currently explored targets and their correlation to the level of difficulty for target exploration are analyzed. From these characteristics, simple rules can be derived for estimating the difficulty level of target exploration. The feasibility of predicting druggable proteins by using simple rules and sequence-derived physicochemical properties is also discussed.