Table 2.
Traffic Light Definitions for Target Assessment Used in the Drug Discovery Unit at the University of Dundee.
| Criterion | Red | Amber | Green |
|---|---|---|---|
| Target validation | No or weak evidence that the target is essential for growth or survival | Either genetic or chemical evidence that target is essential for growth or survival a | Genetic and chemical evidence that target is essential for growth or survival a |
| Druggability | No drug-like inhibitors are known and active site of target is not druggable | Drug-like inhibitors are known or active site potentially druggable | Drug-like inhibitors are known and druggable active site (i.e. clinical precedent within the target family) |
| Assay feasibility | No in vitro assay developed and / or significant problems with reagents (cost or supply) | In vitro assay exists, development into plate format feasible, but not achieved | Assay ready in plate format and protein supply assured within appropriate timelines |
| Toxicity | Human homologue present and little or no structural or chemical evidence that selective inhibition is possible | Human homologue present, but some structural or chemical evidence that selective inhibition is possible | No human homologue present or human homologue known to be non-essential |
| Resistance potential | Target has multiple gene copies or isoforms within same species and is subject to escape from inhibition b | Target has isoforms within same species or may be subject to escape from inhibition b | Target has no known isoforms within same species and is not subject to escape from inhibition b |
| Structural information | No structure of target or closely related homologue | Structure without ligand available and / or poor resolution (> 2.3 Å) or opportunity to build a good homology model | Ligand bound structure of target (or ligand in closely related homologue) available at high resolution (< 2.3 Å) |
a
See Table 3 for the relative merits of genetic and chemical validation.
b
Possible resistance mechanisms include: accumulation of substrate that could reverse inhibition; or target can be deleted, readily modified by point mutation, readily amplified or bypassed.