Chemical probes vs. drugs

I came across this nice blog post on Chemical probes vs. drugs, and I think it touches an important issue. Several (mainly academic) groups identifying hits on novel targets with a suboptimal property profile. Some hits contain reactive functional groups or have an extreme lipophilicity. In these cases, it is always advisable to check the specificity of the hits as the compounds can actually bind to many targets and for example phenotypic effects might be due to other mechanism of action than the target in focus. Both reactive functional groups and high lipophilicity can be associated with selectivity issues and therefore they are less favored for further exploration. But there is a commonly used excuse for "ugly" compounds: that even though they are not fulfilling the criteria for entering into a drug discovery project, they are still useful "tool compounds" or "chemical probes". In the light of the cited Nature paper (very nice title btw: "Stay on target"), this should be reconsidered, as a chemical probe should be even more selective than drug candidates. I think this is worth remembering when dealing with results obtained with less nice compounds. Specificity should be tested at least on a basic level.