Hajduk summarizes the advantages of FBS:
Fragment libraries are more diverse, synthetic resources are used more efficiently and the leads identified from FBS are more likely to yield drug candidates that have optimal physico-chemical properties.He also points out that fragment-based approaches have led to a number of drugs in the clinic.
In the spirit of “vigorous debate,” Hajduk also takes aim at DOS. In comparison with fragment-based approaches, which start with small libraries of small fragments, DOS generally makes use of larger libraries of structurally diverse molecules which are usually drug-sized and are often inspired by natural products. However, Hajduk alleges that:
Most compounds in DOS libraries would be excluded from many corporate screening collections because of their poor physico-chemical properties.I don’t know about “most”, but I will say that many DOS compounds look suspiciously like PAINS. Still, DOS does have at least one strength: FBS is generally limited to well-characterized systems with purified proteins, whereas DOS libraries can be used in complex phenotypic assays where the target may not be known. Whether these will ultimately yield new drugs remains to be seen.
What do you think?