Rear-view Mirrors and Crystal Balls: A Brief Reflection on Drug Discovery

Potential Targeting of Receptors and Signaling Pathways. Although we often think of drugs in terms of pathway A, where the drug blocks the ligand interaction with the receptor, many different sites of action can be considered. Some targets will be more “druggable” than others, which may assist in refining the approach for any particular disease process. In many situations, however, the detailed kinetics of the pathway and the collateral signaling effectors are unknown, making a decision problematic. In some cases, it may be desirable to disrupt the pathway at several levels to ensure effective disruption and to reduce the likelihood of pathway disruption compensation or drug resistance. In other cases, disruption of one pathway may lead to unwanted toxicities.