Target Hypothesis

Drug targets fall into one of three main classes

1. Proteins: hormone receptors, enzymes, ion channels
2. DNA targets
3. RNA and ribosomal targets

Most current drugs are aimed at protein targets.  However, current existing therapies only hit about 400 different drug targets out of an estimated pool ten times this size.

Choosing a drug target

Choosing targets can involve several different approaches.

1. Clinical observation can suggest routes for improving known drugs or new uses for existing agents
2. The Physiological Approach involves designing and screening compounds based on an understanding of basic biochemical and physiological processes. In cases where these are not already known, biological readout from a disease phenotype in an animal model or a cell-based assay can be used to provide details of the mechanism of action and the nature of the target based on the pharmacology of the lead compounds.
3. The target-based approach has been driven by the genomics revolution and begins with identifying the function of a possible therapeutic target by comparing its role in healthy versus diseased organisms. However, this link is not always straightforward and does not always produce the intended therapeutic value in humans.

What is a “Druggable” target?

Assessing “druggability” of a target is somewhat subjective and involves considering factors such as the location of the target in the cell, available routes of administration, possible toxicity and the likelihood of resistance emerging.  It can also represent an assessment of target protein for its potential to selectively bind low-molecular-weight compounds.  However, some targets that were previously deemed undruggable, such as those involving protein-protein interactions, are beginning to bear fruit and may have huge therapeutic potential.

At this stage, the search for initial hit compounds that modulate these processes begins.